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  • 1.
    Aguilo, Francesca
    et al.
    Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
    Zakirova, Zuchra
    Nolan, Katie
    Wagner, Ryan
    Sharma, Rajal
    Hogan, Megan
    Wei, Chengguo
    Sun, Yifei
    Walsh, Martin J.
    Kelley, Kevin
    Zhang, Weijia
    Ozelius, Laurie J.
    Gonzalez-Alegre, Pedro
    Zwaka, Thomas P.
    Ehrlich, Michelle E.
    THAP1: role in mouse embryonic stem cell survival and differentiation2017Inngår i: Stem Cell Reports, ISSN 2213-6711, Vol. 9, nr 1, s. 92-107Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    THAP1 (THAP [Thanatos-associated protein] domain-containing, apoptosis-associated protein 1) is a ubiquitously expressed member of a family of transcription factors with highly conserved DNA-binding and protein-interacting regions. Mutations in THAP1 cause dystonia, DYT6, a neurologic movement disorder. THAP1 downstream targets and the mechanism via which it causes dystonia are largely unknown. Here, we show that wild-type THAP1 regulates embryonic stem cell (ESC) potential, survival, and proliferation. Our findings identify THAP1 as an essential factor underlying mouse ESC survival and to some extent, differentiation, particularly neuroectodermal. Loss of THAP1 or replacement with a disease-causing mutation results in an enhanced rate of cell death, prolongs Nanog, Prdm14, and/or Rex1 expression upon differentiation, and results in failure to upregulate ectodermal genes. ChIP-Seq reveals that these activities are likely due in part to indirect regulation of gene expression.

    Fulltekst (pdf)
    fulltext
  • 2.
    Alkhori, Liza
    et al.
    Linköpings universitet, Avdelningen för cellbiologi.
    Öst, Anita
    Linköpings universitet, Avdelningen för cellbiologi.
    Alenius, Mattias
    Linköpings universitet, Avdelningen för cellbiologi.
    The corepressor Atrophin specifies odorant receptor expression in Drosophila2014Inngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 28, nr 3, s. 1355-1364Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In both insects and vertebrates, each olfactory sensory neuron (OSN) expresses one odorant receptor (OR) from a large genomic repertoire. How a receptor is specified is a tantalizing question addressing fundamental aspects of cell differentiation. Here, we demonstrate that the corepressor Atrophin (Atro) segregates OR gene expression between OSN classes in Drosophila. We show that the knockdown of Atro result in either loss or gain of a broad set of ORs. Each OR phenotypic group correlated with one of two opposing Notch fates, Notch responding, Nba (N(on)), and nonresponding, Nab (N(off)) OSNs. Our data show that Atro segregates ORs expressed in the Nba OSN classes and helps establish the Nab fate during OSN development. Consistent with a role in recruiting histone deacetylates, immunohistochemistry revealed that Atro regulates global histone 3 acetylation (H3ac) in OSNs and requires Hdac3 to segregate OR gene expression. We further found that Nba OSN classes exhibit variable but higher H3ac levels than the Nab OSNs. Together, these data suggest that Atro determines the level of H3ac, which ensures correct OR gene expression within the Nba OSNs. We propose a mechanism by which a single corepressor can specify a large number of neuron classes.-Alkhori, L., Öst, A., Alenius, M. The corepressor Atrophin specifies odorant receptor expression in Drosophila.

  • 3. Andreae, Laura C
    et al.
    Peukert, Daniela
    Lumsden, Andrew
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Analysis of Lrrn1 expression and its relationship to neuromeric boundaries during chick neural development2007Inngår i: Neural Development, ISSN 1749-8104, Vol. 2, nr 22, s. 1-16Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The Drosophila leucine-rich repeat proteins Tartan (TRN) and Capricious (CAPS) mediate cell affinity differences during compartition of the wing imaginal disc. This study aims to identify and characterize the expression of a chick orthologue of TRN/CAPS and examine its potential function in relation to compartment boundaries in the vertebrate central nervous system.

    RESULTS: We identified a complementary DNA clone encoding Leucine-rich repeat neuronal 1 (Lrrn1), a single-pass transmembrane protein with 12 extracellular leucine-rich repeats most closely related to TRN/CAPS. Lrrn1 is dynamically expressed during chick development, being initially localized to the neural plate and tube, where it is restricted to the ventricular layer. It becomes downregulated in boundaries following their formation. In the mid-diencephalon, Lrrn1 expression prefigures the position of the anterior boundary of the zona limitans intrathalamica (ZLI). It becomes progressively downregulated from the presumptive ZLI just before the onset of expression of the signalling molecule Sonic hedgehog (Shh) within the ZLI. In the hindbrain, downregulation at rhombomere boundaries correlates with the emergence of specialized boundary cell populations, in which it is subsequently reactivated. Immunocolocalization studies confirm that Lrrn1 protein is endocytosed from the plasma membrane and is a component of the endosomal system, being concentrated within the early endosomal compartment.

    CONCLUSION: Chick Lrrn1 is expressed in ventricular layer neuroepithelial cells and is downregulated at boundary regions, where neurogenesis is known to be delayed, or inhibited. The timing of Lrrn1 downregulation correlates closely with the activation of signaling molecule expression at these boundaries. This expression is consistent with the emergence of secondary organizer properties at boundaries and its endosomal localisation suggests that Lrrn1 may regulate the subcellular localisation of specific components of signalling or cell-cell recognition pathways in neuroepithelial cells.

  • 4.
    Berghard, Anna
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Hägglund, Anna-Carin
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Bohm, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Carlsson, Leif
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Lhx2-dependent specification of olfactory sensory neurons is required for successful integration of olfactory, vomeronasal, and GnRH neurons2012Inngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 26, nr 8, s. 3464-3472Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Inactivation of the LIM-homeodomain 2 gene (Lhx2) results in a severe defect in specification of olfactory sensory neurons (OSNs). However, the ramifications of lack of Lhx2-dependent OSN specification for formation of the primary olfactory pathway have not been addressed, since mutant mice die in utero. We have analyzed prenatal and postnatal consequences of conditionally inactivating Lhx2 selectively in OSNs. A cell-autonomous effect is that OSN axons cannot innervate their target, the olfactory bulb. Moreover, the lack of Lhx2 in OSNs causes unpredicted, non-cell-autonomous phenotypes. First, the olfactory bulb shows pronounced hypoplasia in adults, and the data suggest that innervation by correctly specified OSNs is necessary for adult bulb size and organization. Second, absence of an olfactory nerve in the conditional mutant reveals that the vomeronasal nerve is dependent on olfactory nerve formation. Third, the lack of a proper vomeronasal nerve prevents migration of gonadotropin-releasing hormone (GnRH) cells the whole distance to their final positions in the hypothalamus during embryo development. As adults, the conditional mutants do not pass puberty, and these findings support the view of an exclusive nasal origin of GnRH neurons in the mouse. Thus, Lhx2 in OSNs is required for functional development of three separate systems.—Berghard, A., Hägglund, A.-C., Bohm, S., and Carlsson, L. Lhx2-dependent specification of olfactory sensory neurons is required for successful integration of olfactory, vomeronasal, and GnRH neurons.

  • 5. Bhalerao, Rishikesh P
    et al.
    Eklöf, Jan
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, The Swedish University of Agricultural Sciences, SE-901 83, Umeå, Sweden.
    Ljung, Karin
    Marchant, Alan
    Bennett, Malcolm
    Sandberg, Göran
    Shoot-derived auxin is essential for early lateral root emergence in Arabidopsis seedlings2002Inngår i: The Plant Journal, ISSN 0960-7412, E-ISSN 1365-313X, Vol. 29, nr 3, s. 325-332Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lateral root formation is profoundly affected by auxins. Here we present data which indicate that light influences the formation of indole-3-acetic acid (IAA) in germinating Arabidopsis seedlings. IAA transported from the developing leaves to the root system is detectable as a short-lived pulse in the roots and is required for the emergence of the lateral root primordia (LRP) during early seedling development. LRP emergence is inhibited by the removal of apical tissues prior to detection of the IAA pulse in the root, but this treatment has minimal effects on LRP initiation. Our results identify the first developing true leaves as the most likely source for the IAA required for the first emergence of the LRP, as removal of cotyledons has only a minor effect on LRP emergence in contrast to removal of the leaves. A basipetal IAA concentration gradient with high levels of IAA in the root tip appears to control LRP initiation, in contrast to their emergence. A significant increase in the ability of the root system to synthesize IAA is observed 10 days after germination, and this in turn is reflected in the reduced dependence of the lateral root emergence on aerial tissue-derived auxin at this stage. We propose a model for lateral root formation during early seedling development that can be divided into two phases: (i) an LRP initiation phase dependent on a root tip-localized IAA source, and (ii) an LRP emergence phase dependent on leaf-derived IAA up to 10 days after germination.

  • 6.
    Boija, Ann
    et al.
    Dept. of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, SE-10691 Stockholm, Sweden.
    Holmqvist, Per-Henrik
    Dept. of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, SE-10691 Stockholm, Sweden.
    Philip, Philge
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Computational Life Science Cluster (CLiC), Umeå, Sweden.
    Zare, Aman
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Computational Life Science Cluster (CLiC), Umeå, Sweden.
    Meyers, David J.
    Dept. Pharmacology and Molecular Sciences, The Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
    Cole, Philip A.
    Dept. Pharmacology and Molecular Sciences, The Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
    Stenberg, Per
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Division of CBRN Defence and Security, FOI, Swedish Defence Research Agency, Sweden.
    Mannervik, Mattias
    Dept. of Molecular Biosciences, the Wenner-Gren Institute, Stockholm University, SE-10691 Stockholm, SwedenDept. Pharmacology and Molecular Sciences, The Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
    Drosophila CBP cooperates with GAGA factor to induce high levels of Pol II promoter-proximal pausingManuskript (preprint) (Annet vitenskapelig)
  • 7. Bonn, Stefan
    et al.
    Zinzen, Robert P
    Girardot, Charles
    Gustafson, E Hilary
    Perez-Gonzalez, Alexis
    Delhomme, Nicolas
    Ghavi-Helm, Yad
    Wilczyński, Bartek
    Riddell, Andrew
    Furlong, Eileen E M
    Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development.2012Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 44, nr 2Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chromatin modifications are associated with many aspects of gene expression, yet their role in cellular transitions during development remains elusive. Here, we use a new approach to obtain cell type-specific information on chromatin state and RNA polymerase II (Pol II) occupancy within the multicellular Drosophila melanogaster embryo. We directly assessed the relationship between chromatin modifications and the spatio-temporal activity of enhancers. Rather than having a unique chromatin state, active developmental enhancers show heterogeneous histone modifications and Pol II occupancy. Despite this complexity, combined chromatin signatures and Pol II presence are sufficient to predict enhancer activity de novo. Pol II recruitment is highly predictive of the timing of enhancer activity and seems dependent on the timing and location of transcription factor binding. Chromatin modifications typically demarcate large regulatory regions encompassing multiple enhancers, whereas local changes in nucleosome positioning and Pol II occupancy delineate single active enhancers. This cell type-specific view identifies dynamic enhancer usage, an essential step in deciphering developmental networks.

  • 8. Brend, Tim
    et al.
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Summerbell, Dennis
    Rigby, Peter W J
    Multiple levels of transcriptional and post-transcriptional regulation are required to define the domain of Hoxb4 expression2003Inngår i: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 130, nr 12, s. 2717-2728Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hox genes are key determinants of anteroposterior patterning of animal embryos, and spatially restricted expression of these genes is crucial to this function. In this study, we demonstrate that expression of Hoxb4 in the paraxial mesoderm of the mouse embryo is transcriptionally regulated in several distinct phases, and that multiple regulatory elements interact to maintain the complete expression domain throughout embryonic development. An enhancer located within the intron of the gene (region C) is sufficient for appropriate temporal activation of expression and the establishment of the correct anterior boundary in the paraxial mesoderm (somite 6/7). However, the Hoxb4 promoter is required to maintain this expression beyond 8.5 dpc. In addition, sequences within the 3' untranslated region (region B) are necessary specifically to maintain expression in somite 7 from 9.0 dpc onwards. Neither the promoter nor region B can direct somitic expression independently, indicating that the interaction of regulatory elements is crucial for the maintenance of the paraxial mesoderm domain of Hoxb4 expression. We further report that the domain of Hoxb4 expression is restricted by regulating transcript stability in the paraxial mesoderm and by selective translation and/or degradation of protein in the neural tube. Moreover, the absence of Hoxb4 3'-untranslated sequences from transgene transcripts leads to inappropriate expression of some Hoxb4 transgenes in posterior somites, indicating that there are sequences within region B that are important for both transcriptional and post-transcriptional regulation.

  • 9. Broom, Emma R
    et al.
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Butts, Thomas
    Campo-Paysaa, Florent
    Wingate, Richard J T
    The roof plate boundary is a bi-directional organiser of dorsal neural tube and choroid plexus development.2012Inngår i: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 139, nr 22, s. 4261-4270Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The roof plate is a signalling centre positioned at the dorsal midline of the central nervous system and generates dorsalising morphogenic signals along the length of the neuraxis. Within cranial ventricles, the roof plate gives rise to choroid plexus, which regulates the internal environment of the developing and adult brain and spinal cord via the secretion of cerebrospinal fluid. Using the fourth ventricle as our model, we show that the organiser properties of the roof plate are determined by its boundaries with the adjacent neuroepithelium. Through a combination of in ovo transplantation, co-culture and electroporation techniques in chick embryos between embryonic days 3 and 6, we demonstrate that organiser properties are maintained by interactions between the non-neural roof plate and the neural rhombic lip. At the molecular level, this interaction is mediated by Delta-Notch signalling and upregulation of the chick homologue of Hes1: chairy2. Gain- and loss-of-function approaches reveal that cdelta1 is both necessary and sufficient for organiser function. Our results also demonstrate that while chairy2 is specifically required for the maintenance of the organiser, its ectopic expression is not sufficient to recapitulate organiser properties. Expression of atonal1 in the rhombic lip adjacent at the roof plate boundary is acutely dependent on both boundary cell interactions and Delta-Notch signalling. Correspondingly, the roof plate boundary organiser also signals to the roof plate itself to specify the expression of early choroid plexus markers. Thus, the roof plate boundary organiser signals bi-directionally to acutely coordinate the development of adjacent neural and non-neural tissues.

  • 10.
    Brunoni, Federica
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå Plant Science Centre, Department of Forest Genetics and PlantPhysiology, Swedish University of Agricultural Sciences (SLU), 90183, Umeå, Sweden.
    Collani, Silvio
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Casanova-Saez, Ruben
    Simura, Jan
    Karady, Michal
    Schmid, Markus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Ljung, Karin
    Bellini, C
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Institut Jean-Pierre Bourgin, INRAE, AgroParisTech, Université Paris-Saclay, 78000, Versailles, France.
    Conifers exhibit a characteristic inactivation of auxin to maintain tissue homeostasis2020Inngår i: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 226, nr 6, s. 1753-1765Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Dynamic regulation of the concentration of the natural auxin (IAA) is essential to coordinate most of the physiological and developmental processes and responses to environmental changes. Oxidation of IAA is a major pathway to control auxin concentrations in angiosperms and, along with IAA conjugation, to respond to perturbation of IAA homeostasis. However, these regulatory mechanisms remain poorly investigated in conifers. To reduce this knowledge gap, we investigated the different contributions of the IAA inactivation pathways in conifers. MS-based quantification of IAA metabolites under steady-state conditions and after perturbation was investigated to evaluate IAA homeostasis in conifers. Putative Picea abies GH3 genes (PaGH3) were identified based on a comprehensive phylogenetic analysis including angiosperms and basal land plants. Auxin-inducible PaGH3 genes were identified by expression analysis and their IAA-conjugating activity was explored. Compared to Arabidopsis, oxidative and conjugative pathways differentially contribute to reduce IAA concentrations in conifers. We demonstrated that the oxidation pathway plays a marginal role in controlling IAA homeostasis in spruce. By contrast, an excess of IAA rapidly activates GH3-mediated irreversible conjugation pathways. Taken together, these data indicate that a diversification of IAA inactivation mechanisms evolved specifically in conifers.

    Fulltekst (pdf)
    fulltext
  • 11.
    Burguière, Anne-Cecile
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Nord, Hanna
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    von Hofsten, Jonas
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Alkali-like myosin light chain-1 (myl1) is an early marker for differentiating fast muscle cells in zebrafish2011Inngår i: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 240, nr 7, s. 1856-1863Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    During myogenesis, muscle precursors become divided into either fast- or slow-twitch fibres, which in the zebrafish occupy distinct domains in the embryo. Genes encoding sarcomeric proteins specific for fast or slow fibres are frequently used as lineage markers. In an attempt to identify and evaluate early definitive markers for cells in the fast-twitch pathway, we analysed genes encoding proteins contributing to the fast sarcomeric structures. The previously uncharacterized zebrafish alkali-like myosin light chain gene (myl1) was found to be expressed exclusively in cells in the fast-twitch pathway initiated at an early stage of fast fibre differentiation. Myl1 was expressed earlier, and in a more fibre type restricted manner, than any of the previously described and frequently used fast myosin light and heavy chain and troponin muscle markers mylz2, mylz3, tnni2, tnnt3a, fMyHC1.3. In summary, this study introduces a novel marker for early differentiating fast muscle cells.

  • 12. Caballero-Pérez, Juan
    et al.
    Espinal-Centeno, Annie
    Falcon, Francisco
    García-Ortega, Luis F.
    Curiel-Quesada, Everardo
    Cruz-Hernández, Andrés
    Bako, Laszlo
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Chen, Xuemei
    Martínez, Octavio
    Alberto Arteaga-Vázquez, Mario
    Herrera-Estrella, Luis
    Cruz-Ramírez, Alfredo
    Transcriptional landscapes of Axolotl (Ambystoma mexicanum)2018Inngår i: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 433, nr 2, s. 227-239Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The axolotl (Ambystoma mexicanum) is the vertebrate model system with the highest regeneration capacity. Experimental tools established over the past 100 years have been fundamental to start unraveling the cellular and molecular basis of tissue and limb regeneration. In the absence of a reference genome for the Axolotl, transcriptomic analysis become fundamental to understand the genetic basis of regeneration.

    Here we present one of the most diverse transcriptomic data sets for Axolotl by profiling coding and non coding RNAs from diverse tissues. We reconstructed a population of 115,906 putative protein coding mRNAs as full ORFs (including isoforms). We also identified 352 conserved miRNAs and 297 novel putative mature miRNAs.

    Systematic enrichment analysis of gene expression allowed us to identify tissue-specific protein-coding transcripts. We also found putative novel and conserved microRNAs which potentially target mRNAs which are reported as important disease candidates in heart and liver.

  • 13.
    Calderon, Robert H.
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Department of Plant and Microbial Biology, University of California, CA, Berkeley, United States; Plant Gene Expression Center, Agriculture Research Service, US Department of Agriculture, CA, Albany, United States.
    Dalton, Jutta
    Department of Plant and Microbial Biology, University of California, CA, Berkeley, United States; Plant Gene Expression Center, Agriculture Research Service, US Department of Agriculture, CA, Albany, United States.
    Zhang, Yu
    Department of Plant and Microbial Biology, University of California, CA, Berkeley, United States; Plant Gene Expression Center, Agriculture Research Service, US Department of Agriculture, CA, Albany, United States; US Department of Energy, Joint Genome Institute, Lawrence Berkeley National Laboratory, CA, Berkeley, United States.
    Quail, Peter H.
    Department of Plant and Microbial Biology, University of California, CA, Berkeley, United States; Plant Gene Expression Center, Agriculture Research Service, US Department of Agriculture, CA, Albany, United States.
    Shade triggers posttranscriptional PHYTOCHROME-INTERACTING FACTOR-dependent increases in H3K4 trimethylation2022Inngår i: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 190, nr 3, s. 1915-1926Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The phytochrome (phy)-PHYTOCHROME-INTERACTING FACTOR (PIF) sensory module perceives and transduces light signals to direct target genes (DTGs), which then drive the adaptational responses in plant growth and development appropriate to the prevailing environment. These signals include the first exposure of etiolated seedlings to sunlight upon emergence from subterranean darkness and the change in color of the light that is filtered through, or reflected from, neighboring vegetation ("shade"). Previously, we identified three broad categories of rapidly signal-responsive genes: those repressed by light and conversely induced by shade; those repressed by light, but subsequently unresponsive to shade; and those responsive to shade only. Here, we investigate the potential role of epigenetic chromatin modifications in regulating these contrasting patterns of phy-PIF module-induced expression of DTGs in Arabidopsis (Arabidopsis thaliana). Using RNA-seq and ChIP-seq to determine time-resolved profiling of transcript and histone 3 lysine 4 trimethylation (H3K4me3) levels, respectively, we show that, whereas the initial dark-to-light transition triggers a rapid, apparently temporally coincident decline of both parameters, the light-to-shade transition induces similarly rapid increases in transcript levels that precede increases in H3K4me3 levels. Together with other recent findings, these data raise the possibility that, rather than being causal in the shade-induced expression changes, H3K4me3 may function to buffer the rapidly fluctuating shade/light switching that is intrinsic to vegetational canopies under natural sunlight conditions.

    Fulltekst (pdf)
    fulltext
  • 14.
    Chelcea, Ioana C.
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Vogs, Carolina
    Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Hamers, Timo
    Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
    Koekkoek, Jacco
    Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
    Legradi, Jessica
    Amsterdam Institute for Life and Environment (A-LIFE), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
    Sapounidou, Maria
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Örn, Stefan
    Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Andersson, Patrik L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Physiology-informed toxicokinetic model for the zebrafish embryo test: a case study of bisphenolsManuskript (preprint) (Annet vitenskapelig)
  • 15.
    Chen, Sa
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Larsson, Anna L.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Tegeling, Erik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Rasmuson Lestander, Asa
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    In vivo analysis of Suppressor of zeste 12´s different isoformsManuskript (Annet vitenskapelig)
    Abstract [en]

    Polycomb Group (PcG) genes are known to encode a large chromatin-associated family of proteins which are involved in genomic regulation of many cellular processes. Su(z)12 is a key component in PcG silencing. It is needed for three levels of methylation of histone 3 lysine 27 in vivo in Drosophila. Here, we report that Su(z)12 may exist in different isoforms and that these isoforms are spatially and temporally regulated. The biological function of the Su(z)12-A and -B isoforms seems to be very different. For instance the transgenic Su(z)12-B and the human homolog SUZ12, but not Su(z)12-A, rescue Su(z)12 mutants. Furthermore, transgenic flies over-expressing Su(z)12-B show typical homeotic transformation phenotypes, while over-expression of Su(z)12-A does not. However, the two isoforms appears to be able to substitute for each other in some aspects. During larval and pupal stages, Su(z)12-A seems to play the main role. 

  • 16.
    Chen, Sa
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Rasmuson-Lestander, Åsa
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Regulation of the Drosophila engrailed gene by Polycomb repressor complex 22009Inngår i: Mechanisms of Development, ISSN 0925-4773, E-ISSN 1872-6356, Vol. 126, nr 5-6, s. 443-448Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Suppressor-of-zeste-12 (Su(z)12) is a core component of the Polycomb repressive complex 2 (PRC2), which has a methyltransferase activity directed towards lysine residues of histone 3. Mutations in Polycomb group (PcG) genes cause de-repression of homeotic genes and subsequent homeotic transformations. Another target for Polycomb silencing is the engrailed gene, which encodes a key regulator of segmentation in the early Drosophila embryo. In close proximity to the en gene is a Polycomb Response Element, but whether en is regulated by Su(z)12 is not known. In this report, we show that en is not de-repressed in Su(z)12 or Enhancer-of-zeste mutant clones in the anterior compartment of wing discs. Instead, we find that en expression is down-regulated in the posterior portion of wing discs, indicating that the PRC2 complex acts as an activator of en. Our results indicate that this is due to secondary effects, probably caused by ectopic expression of Ubx and Abd-B.

  • 17. Coutinho, Ana P
    et al.
    Borday, Caroline
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Jungbluth, Stefan
    Champagnat, Jean
    Lumsden, Andrew
    Fortin, Gilles
    Induction of a parafacial rhythm generator by rhombomere 3 in the chick embryo.2004Inngår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 24, nr 42, s. 9383-9390Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Observations of knock-out mice suggest that breathing at birth requires correct development of a specific hindbrain territory corresponding to rhombomeres (r) 3 and 4. Focusing on this territory, we examined the development of a neuronal rhythm generator in the chick embryo. We show that rhythmic activity in r4 is inducible after developmental stage 10 through interaction with r3. Although the nature of this interaction remains obscure, we find that the expression of Krox20, a segmentation gene responsible for specifying r3 and r5, is sufficient to endow other rhombomeres with the capacity to induce rhythmic activity in r4. Induction is robust, because it can be reproduced with r2 and r6 instead of r4 and with any hindbrain territory that normally expresses Krox20 (r3, r5) or can be forced to do so (r1, r4). Interestingly, the interaction between r4 and r3/r5 that results in rhythm production can only take place through the anterior border of r4, revealing a heretofore unsuspected polarity in individual rhombomeres. The r4 rhythm generator appears to be homologous to a murine respiratory parafacial neuronal system developing in r4 under the control of Krox20 and Hoxa1. These results identify a late role for Krox20 at the onset of neurogenesis.

  • 18.
    Davies, Wayne I. L.
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Sghari, Soufien
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Upton, Brian A.
    Nord, Christoffer
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Hahn, Max
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Ahlgren, Ulf
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Lang, Richard A.
    Gunhaga, Lena
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Distinct opsin 3 (Opn3) expression in the developing nervous system during mammalian embryogenesis2021Inngår i: eNeuro, E-ISSN 2373-2822, Vol. 8, nr 5, artikkel-id ENEURO.0141-21.2021Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Opsin 3 (Opn3) is highly expressed in the adult brain, however, information for spatial and temporal expression patterns during embryogenesis is significantly lacking. Here, an Opn3-eGFP reporter mouse line was used to monitor cell body expression and axonal projections during embryonic and early postnatal to adult stages. By applying 2D and 3D fluorescence imaging techniques, we have identified the onset of Opn3 expression, which predominantly occurred during embryonic stages, in various structures during brain/head development. In ad-dition, this study defines over twenty Opn3-eGFP-positive neural structures never reported before. Opn3-eGFP was first observed at E9.5 in neural regions, including the ganglia that will ultimately form the trigeminal, facial and vestibulocochlear cranial nerves (CNs). As development proceeds, expanded Opn3-eGFP expression coincided with the formation and maturation of critical components of the central and peripheral nervous systems (CNS, PNS), including various motor-sensory tracts, such as the dorsal column-medial lemniscus (DCML) sensory tract, and olfactory, acoustic, and optic tracts. The widespread, yet distinct, detection of Opn3-eGFP already at early embryonic stages suggests that Opn3 might play important functional roles in the developing brain and spinal cord to regulate multiple motor and sensory circuitry systems, including proprio-ception, nociception, ocular movement, and olfaction, as well as memory, mood, and emotion. This study presents a crucial blueprint from which to investigate autonomic and cognitive opsin-dependent neural development and resultant behaviors under physiological and pathophysiological conditions.

    Fulltekst (pdf)
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  • 19.
    Davoine, Celine
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Abreu, Ilka N.
    Khajeh, Khalil
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Blomberg, Jeanette
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Kidd, Brendan N.
    Kazan, Kemal
    Schenk, Peer M.
    Gerber, Lorenz
    Nilsson, Ove
    Moritz, Thomas
    Björklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Functional metabolomics as a tool to analyze Mediator function and structure in plants2017Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 12, nr 6, artikkel-id e0179640Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mediator is a multiprotein transcriptional co-regulator complex composed of four modules; Head, Middle, Tail, and Kinase. It conveys signals from promoter-bound transcriptional regulators to RNA polymerase II and thus plays an essential role in eukaryotic gene regulation. We describe subunit localization and activities of Mediator in Arabidopsis through metabolome and transcriptome analyses from a set of Mediator mutants. Functional metabolomic analysis based on the metabolite profiles of Mediator mutants using multivariate statistical analysis and heat-map visualization shows that different subunit mutants display distinct metabolite profiles, which cluster according to the reported localization of the corresponding subunits in yeast. Based on these results, we suggest localization of previously unassigned plant Mediator subunits to specific modules. We also describe novel roles for individual subunits in development, and demonstrate changes in gene expression patterns and specific metabolite levels in med18 and med25, which can explain their phenotypes. We find that med18 displays levels of phytoalexins normally found in wild type plants only after exposure to pathogens. Our results indicate that different Mediator subunits are involved in specific signaling pathways that control developmental processes and tolerance to pathogen infections.

    Fulltekst (pdf)
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  • 20. Dhillon, Sundeep S.
    et al.
    Torell, Frida
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Accelerator Lab (ACL), Karlsruhe Institute of Technology, Karlsruhe, Germany; AcureOmics, Umeå, Sweden.
    Donten, Magdalena
    Lundstedt-Enkel, Katrin
    Bennett, Kate
    Raennar, Stefan
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. AcureOmics, Umeå, Sweden.
    Lundstedt, Torbjorn
    Metabolic profiling of zebrafish embryo development from blastula period to early larval stages2019Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 14, nr 5, artikkel-id e0213661Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The zebrafish embryo is a popular model for drug screening, disease modelling and molecular genetics. In this study, samples were obtained from zebrafish at different developmental stages. The stages that were chosen were 3/4, 4/5, 24, 48, 72 and 96 hours post fertilization (hpf). Each sample included fifty embryos. The samples were analysed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). Principle component analysis (PCA) was applied to get an overview of the data and orthogonal projection to latent structure discriminant analysis (OPLS-DA) was utilised to discriminate between the developmental stages. In this way, changes in metabolite profiles during vertebrate development could be identified. Using a GC-TOF-MS metabolomics approach it was found that nucleotides and metabolic fuel (glucose) were elevated at early stages of embryogenesis, whereas at later stages amino acids and intermediates in the Krebs cycle were abundant. This agrees with zebrafish developmental biology, as organs such as the liver and pancreas develop at later stages. Thus, metabolomics of zebrafish embryos offers a unique opportunity to investigate large scale changes in metabolic processes during important developmental stages in vertebrate development. In terms of stability of the metabolic profile and viability of the embryos, it was concluded at 72 hpf was a suitable time point for the use of zebrafish as a model system in numerous scientific applications.

    Fulltekst (pdf)
    fulltext
  • 21.
    Dorafshan Esfahani, Eshagh
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå University.
    Methyltransferase Ash1, histone methylation and their impact on Polycomb repression2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Antagonistic interactions between Polycomb Group (PcG) and Trithorax Group (TrxG) proteins orchestrate the expression of key developmental genes. Distinct maternally loaded repressors establish the silenced state of these genes in cells where they should not be expressed and later PcG proteins sense whether a target gene is inactive and maintain the repression throughout multiple cell divisions. PcG proteins are targeted to genes by DNA elements called Polycomb Response Elements (PREs). The proteins form two major classes of complexes, namely Polycomb Repressive Complex 1 (PRC1) and Polycomb Repressive Complex 2 (PRC2). Mechanistic details of Polycomb repression are not fully understood, however, tri-methylation of Lysine 27 of histone H3 (H3K27me3) is essential for this process. Using Drosophila cell lines deficient for either PRC1 or PRC2, I investigated the role of H3K27 methylation and the interdependence of PRC1 complexes for their recruitment to PREs. My results indicate that recruitment of PcG complexes to PREs proceed via multiple pathways and that H3K27 methylation is not needed for their targeting. However, the methylation is required to stabilize interactions of PRE-anchored PcG complexes with surrounding chromatin.

    TrxG proteins prevent erroneous repression of Polycomb target genes where these genes need to be expressed. Ash1 is a TrxG protein which binds Polycomb target genes when they are transcriptionally active. It contains a SET domain which methylates Lysine 36 of histone H3 (H3K36). In vitro, histone H3 methylated at K36 is a poor substrate for H3K27 methylation by PRC2. This prompted a model where Ash1 counteracts Polycomb repression through H3K36 methylation. However, this model was never tested in vivo and does not consider several experimental observations. First, in the ash1 mutant flies the bulk H3K36me2/H3K36me3 levels remain unchanged. Second, in Drosophila, there are two other H3K36-specific histone methyltransferases, NSD and Set2, which should be capable to inhibit PRC2. Third, Ash1 contains multiple evolutionary conserved domains whose roles have not been investigated. Therefore, I asked whether H3K36 methylation is critical for Ash1 to counteract Polycomb repression in vivo and whether NSD and Set2 proteins contribute to this process. I used flies lacking endogenous histone genes and complemented them with transgenic histone genes where Lysine 36 is replaced by Arginine. In these animals, I assayed erroneous repression of HOX genes as a readout for erroneous Polycomb repression. I used the same readout in the NSD or Set2 mutant flies. I also asked if other conserved domains of Ash1 are essential for its function. In addition to SET and domain, Ash1 contains three AT hook motifs as well as BAH and PHD domains. I genetically complemented ash1 loss of function animals with transgenic Ash1 variants, in each, one domain of Ash1 is deleted. I found that Ash1 is the only H3K36-specific histone methyltransferase which counteracts Polycomb repression in Drosophila. My findings suggest that the model, where Ash1 counteracts PcG repression by inhibiting PRC2 via methylation of H3K36, has to be revised. I also showed that, in vivo, Ash1 acts as a multimer and requires SET, BAH and PHD domains to counteract Polycomb repression.

    This work led to two main conclusions. First, trimethylation of H3K27 is not essential for targeting PcG proteins to PREs but acts afterwards to stabilize their interaction with the chromatin of the neighboring genes. Second, while SET domain is essential for Ash1 to oppose Polycomb repression, methylation of H3K36 does not play a central role in the process.

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  • 22.
    Dorafshan, Eshagh
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Kahn, Tatyana G.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Glotov, Alexander
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Savitsky, Mikhail
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Schwartz, Yuri B.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Genetic Dissection Reveals the Role of Ash1 Domains in Counteracting Polycomb Repression2019Inngår i: G3: Genes, Genomes, Genetics, E-ISSN 2160-1836, Vol. 9, nr 11, s. 3801-3812Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Antagonistic functions of Polycomb and Trithorax proteins are essential for proper development of all metazoans. While the Polycomb proteins maintain the repressed state of many key developmental genes, the Trithorax proteins ensure that these genes stay active in cells where they have to be expressed. Ash1 is the Trithorax protein that was proposed to counteract Polycomb repression by methylating lysine 36 of histone H3. However, it was recently shown that genetic replacement of Drosophila histone H3 with the variant that carried Arginine instead of Lysine at position 36 did not impair the ability of Ash1 to counteract Polycomb repression. This argues that Ash1 counteracts Polycomb repression by methylating yet unknown substrate(s) and that it is time to look beyond Ash1 methyltransferase SET domain, at other evolutionary conserved parts of the protein that received little attention. Here we used Drosophila genetics to demonstrate that Ash1 requires each of the BAH, PHD and SET domains to counteract Polycomb repression, while AT hooks are dispensable. Our findings argue that, in vivo, Ash1 acts as a multimer. Thereby it can combine the input of the SET domain and PHD-BAH cassette residing in different peptides. Finally, using new loss of function alleles, we show that zygotic Ash1 is required to prevent erroneous repression of homeotic genes of the bithorax complex in the embryo.

  • 23.
    Dorafshan, Eshagh
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Kahn, Tatyana G.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Glotov, Alexander
    Savitsky, Mikhail
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Walther, Matthias
    Reuter, Gunter
    Schwartz, Yuri B.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Does Ash1 counteract Polycomb repression by methylating H3K36?Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Polycomb repression is critical to maintain cell type specific genome expression programs in a wide range of multicellular animals. Equally important but less studied is the Trithorax group system, which safeguards Polycomb target genes from the repression in cells where they have to remain active. Based on in vitro studies it was proposed that the Trithorax group system acts via methylation of histone H3 at Lysine 4 (H3K4) and Lysine 36 (H3K36) thereby inhibiting histone methyltransferase activity of the Polycomb complexes. This hypothesis is yet to be comprehensively tested in vivo. Here we used the power of the Drosophila model to investigate how the Trithorax group protein Ash1 and the H3K36 methylation counteract Polycomb repression. We show, for the first time, that Ash1 is the only Drosophila H3K36-specific methyltransferase required to prevent excessive Polycomb repression of homeotic genes. Unexpectedly, our experiments revealed no correlation between the extent of H3K36 methylation and the resistance to Polycomb repression. Furthermore, we find that complete substitution of the zygotic histone H3 with a variant in which Lysine 36 is replaced by Arginine does not cause excessive repression of Drosophila homeotic genes. Together with earlier studies, our results suggest that the model, where the Trithorax group proteins methylate histone H3 to inhibit the histone methyltransferase activity of the Polycomb complexes, may need to be reevaluated.

  • 24.
    Dorafshan, Eshagh
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Kahn, Tatyana G.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Schwartz, Yuri B.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Hierarchical recruitment of Polycomb complexes revisited2017Inngår i: Nucleus, ISSN 1949-1034, E-ISSN 1949-1042, Vol. 8, nr 5, s. 496-505Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Polycomb Group (PcG) proteins epigenetically repress key developmental genes and thereby control alternative cell fates. PcG proteins act as complexes that can modify histones and these histone modifications play a role in transmitting the memory of the repressed state as cells divide. Here we consider mainstream models that link histone modifications to hierarchical recruitment of PcG complexes and compare them to results of a direct test of interdependence between PcG complexes for recruitment to Drosophila genes. The direct test indicates that PcG complexes do not rely on histone modifications to recognize their target genes but use them to stabilize the interactions within large chromatin domains. It also shows that multiple strategies are used to coordinate the targeting of PcG complexes to different genes, which may make the repression of these genes more or less robust.

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    fulltext
  • 25.
    Dubreuil, Carole
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Ji, Yan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Strand, Åsa
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Grönlund, Andreas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    A quantitative model of the phytochrome-PIF light signalling initiating chloroplast development2017Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 7, artikkel-id 13884Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The components required for photosynthesis are encoded in two separate genomes, the nuclear and the plastid. To address how synchronization of the two genomes involved can be attained in early light-signalling during chloroplast development we have formulated and experimentally tested a mathematical model simulating light sensing and the following signalling response. The model includes phytochrome B (PhyB), the phytochrome interacting factor 3 (PIF3) and putative regulatory targets of PIF3. Closed expressions of the phyB and PIF3 concentrations after light exposure are derived, which capture the relevant timescales in the response of genes regulated by PIF3. Sequence analysis demonstrated that the promoters of the nuclear genes encoding sigma factors (SIGs) and polymerase-associated proteins (PAPs) required for expression of plastid encoded genes, contain the cis-elements for binding of PIF3. The model suggests a direct link between light inputs via PhyB-PIF3 to the plastid transcription machinery and control over the expression of photosynthesis components both in the nucleus and in the plastids. Using a pluripotent Arabidopsis cell culture in which chloroplasts develop from undifferentiated proplastids following exposure to light, we could experimentally verify that the expression of SIGs and PAPs in response to light follow the calculated expression of a PhyB-PIF3 regulated gene.

    Fulltekst (pdf)
    fulltext
  • 26.
    Dubreuil, Carole
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå 901 83, Sweden.
    Jin, Xu
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå 901 83, Sweden.
    Grönlund, Andreas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Fischer, Urs
    A local auxin gradient regulates root cap self-renewal and size homeostasis2018Inngår i: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 28, nr 16, s. 2581-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Organ size homeostasis, compensatory growth to replace lost tissue, requires constant measurement of size and adjustment of growth rates. Morphogen gradients control organ and tissue sizes by regulating stem cell activity, cell differentiation, and removal in animals [1-3]. In plants, control of tissue size is of specific importance in root caps to protect the growing root tip from mechanical damage [4]. New root cap tissue is formed by the columella and lateral root-cap-epidermal stem cells, whose activity is regulated through non-dividing niche-like cells, the quiescent center (QC) [4, 5]. Columella daughter cells in contact with the QC retain the potency to divide, while derivatives oriented toward the mature cap undergo differentiation. The outermost columella layers are sequentially separated from the root body, involving remodeling of cell walls [6]. Factors regulating the balance between cell division, elongation, and separation to keep root cap size constant are currently unknown [4]. Here, we report that stem cell proliferation induced cell separation at the periphery of the root cap, resulting in tissue size homeostasis. An auxin response gradient with a maximum in the QC and a minimum in the detaching layer was established prior to the onset of cell separation. In agreement with a mathematical model, tissue size was positively regulated by the amount of auxin released from the source. Auxin transporters localized non-polarly to plasma membranes of the inner cap, partly isolating separating layers from the auxin source. Together, these results are in support of an auxin gradient measuring and regulating tissue size.

  • 27.
    Eklöf, Jan
    Institutionen för skoglig genetik och växtfysiologi, Sveriges lantbruksuniversitet, 901 83 Umeå.
    Control of lateral root development in Arabidopsis thaliana2001Licentiatavhandling, med artikler (Annet vitenskapelig)
  • 28. Engelhorn, Julia
    et al.
    Blanvillain, Robert
    Kroner, Christian
    Parrinello, Hugues
    Rohmer, Marine
    Pose, David
    Ott, Felix
    Schmid, Markus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Department of Molecular Biology, Max Planck Institute for Developmental Biology, Tübingen, Germany.
    Carles, Cristel C.
    Dynamics of H3K4me3 Chromatin Marks Prevails over H3K27me3 for Gene Regulation during Flower Morphogenesis in Arabidopsis thaliana2017Inngår i: Epigenomes, ISSN 2075-4655, Vol. 1, nr 2, artikkel-id 8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Plant life-long organogenesis involves sequential, time and tissue specific expression of developmental genes. This requires activities of Polycomb Group (PcG) and trithorax Group complexes (trxG), respectively responsible for repressive Histone 3 trimethylation at lysine 27 (H3K27me3) and activation-related Histone 3 trimethylation at lysine 4 (H3K4me3). However, the genome-wide dynamics in histone modifications that occur during developmental processes have remained elusive. Here, we report the distributions of H3K27me3 and H3K4me3 along with expression changes, in a developmental series including Arabidopsis thaliana leaf and three stages of flower development. We found that chromatin mark levels are highly dynamic over the time series on nearly half of all Arabidopsis genes. Moreover, during early flower morphogenesis, changes in H3K4me3 prevail over changes in H3K27me3 and quantitatively correlate with expression changes, while H3K27me3 changes occur later. Notably, we found that H3K4me3 increase during the early activation of PcG target genes while H3K27me3 level remain relatively constant at the locus. Our results reveal that H3K4me3 predicts changes in gene expression better than H3K27me3, unveil unexpected chromatin mechanisms at gene activation and underline the relevance of tissue-specific temporal epigenomics.

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  • 29.
    Escamez, Sacha
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    André, Domenique
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Sztojka, Bernadette
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Bollhöner, Benjamin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Hall, Hardy
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Berthet, Béatrice
    Voss, Ute
    Lers, Amnon
    Maizel, Alexis
    Andersson, Magnus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Bennett, Malcolm
    Tuominen, Hannele
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Cell Death in Cells Overlying Lateral Root Primordia Facilitates Organ Growth in Arabidopsis2020Inngår i: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 30, nr 3, s. 455-464Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Plant organ growth is widely accepted to be determined by cell division and cell expansion, but, unlike that in animals, the contribution of cell elimination has rarely been recognized. We investigated this paradigm during Arabidopsis lateral root formation, when the lateral root primordia (LRP) must traverse three overlying cell layers within the parent root. A subset of LRP-overlying cells displayed the induction of marker genes for cell types undergoing developmental cell death, and their cell death was detected by electron, confocal, and light sheet microscopy techniques. LRP growth was delayed in cell-deathdeficient mutants lacking the positive cell death regulator ORESARA1/ANAC092 (ORE1). LRP growth was restored in ore1-2 knockout plants by genetically inducing cell elimination in cells overlying the LRP or by physically killing LRP-overlying cells by ablation with optical tweezers. Our results support that, in addition to previously discovered mechanisms, cell elimination contributes to regulating lateral root emergence.

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  • 30. Espinal-Centeno, Annie
    et al.
    Dipp-Alvarez, Melissa
    Saldana, Carlos
    Bako, Laszlo
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Cruz-Ramirez, Alfredo
    Conservation analysis of core cell cycle regulators and their transcriptional behavior during limb regeneration in Ambystoma mexicanum2020Inngår i: Mechanisms of Development, ISSN 0925-4773, E-ISSN 1872-6356, Vol. 164, artikkel-id 103651Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ambystoma mexicanum (axolotl) has been one of the major experimental models for the study of regeneration during the past 100 years. Axolotl limb regeneration takes place through a multi-stage and complex developmental process called epimorphosis that involves diverse events of cell reprogramming. Such events start with dedifferentiation of somatic cells and the proliferation of quiescent stem cells to generate a population of proliferative cells called blastema. Once the blastema reaches a mature stage, cells undergo progressive differentiation into the diverse cell lineages that will form the new limb. Such pivotal cell reprogramming phenomena depend on the fine-tuned regulation of the cell cycle in each regeneration stage, where cell populations display specific proliferative capacities and differentiation status. The axolotl genome has been fully sequenced and released recently, and diverse RNA-seq approaches have also been generated, enabling the identification and conservatory analysis of core cell cycle regulators in this species. We report here our results from such analyses and present the transcriptional behavior of key regulatory factors during axolotl limb regeneration. We also found conserved protein interactions between axolotl Cyclin Dependent Kinases 2, 4 and 6 and Cyclins type D and E. Canonical CYC-CDK interactions that play major roles in modulating cell cycle progression in eukaryotes.

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  • 31. Gendre, Delphine
    et al.
    Baral, Anirban
    Dang, Xie
    Esnay, Nicolas
    Boutté, Yohann
    Stanislas, Thomas
    Vain, Thomas
    Claverol, Stéphane
    Gustavsson, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Lin, Deshu
    Grebe, Markus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Institute of Biochemistry and Biology, Plant Physiology, Universityof Potsdam, Germany.
    Bhalerao, Rishikesh P.
    Rho-of-plant activated root hair formation requires Arabidopsis YIP4a/b gene function2019Inngår i: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 146, nr 5, artikkel-id dev168559Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Root hairs are protrusions from root epidermal cells with crucial roles in plant soil interactions. Although much is known about patterning, polarity and tip growth of root hairs, contributions of membrane trafficking to hair initiation remain poorly understood. Here, we demonstrate that the trans-Golgi network-localized YPT-INTERACTING PROTEIN 4a and YPT-INTERACTING PROTEIN 4b (YIP4a/b) contribute to activation and plasma membrane accumulation of Rho-of-plant (ROP) small GTPases during hair initiation, identifying YIP4a/b as central trafficking components in ROP-dependent root hair formation.

    Fulltekst (pdf)
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  • 32.
    Gilthorpe, Jonathan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Papantoniou, Elli-Kalliopi
    Chédotal, Alain
    Lumsden, Andrew
    Wingate, Richard J T
    The migration of cerebellar rhombic lip derivatives.2002Inngår i: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 129, nr 20, s. 4719-4728Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have used cell labelling, co-culture and time-lapse confocal microscopy to investigate tangential neuronal migration from the rhombic lip. Cerebellar rhombic lip derivatives demonstrate a temporal organisation with respect to their morphology and response to migration cues. Early born cells, which migrate into ventral rhombomere 1, have a single long leading process that turns at the midline and becomes an axon. Later born granule cell precursors also migrate ventrally but halt at the lateral edge of the cerebellum, correlating with a loss of sensitivity to netrin 1 and expression of Robo2. The rhombic lip and ventral midline express Slit2 and both early and late migrants are repelled by sources of Slit2 in co-culture. These studies reveal an intimate relationship between birthdate, response to migration cues and neuronal fate in an identified population of migratory cells. The use of axons in navigating cell movement suggests that tangential migration is an elaboration of the normal process of axon extension.

  • 33.
    Gilthorpe, Jonathan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vandromme, Marie
    Brend, Tim
    Gutman, Alejandro
    Summerbell, Dennis
    Totty, Nick
    Rigby, Peter W J
    Spatially specific expression of Hoxb4 is dependent on the ubiquitous transcription factor NFY.2002Inngår i: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 129, nr 16, s. 3887-99Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Understanding how boundaries and domains of Hox gene expression are determined is critical to elucidating the means by which the embryo is patterned along the anteroposterior axis. We have performed a detailed analysis of the mouse Hoxb4 intron enhancer to identify upstream transcriptional regulators. In the context of an heterologous promoter, this enhancer can establish the appropriate anterior boundary of mesodermal expression but is unable to maintain it, showing that a specific interaction with its own promoter is important for maintenance. Enhancer function depends on a motif that contains overlapping binding sites for the transcription factors NFY and YY1. Specific mutations that either abolish or reduce NFY binding show that it is crucial for enhancer activity. The NFY/YY1 motif is reiterated in the Hoxb4 promoter and is known to be required for its activity. As these two factors are able to mediate opposing transcriptional effects by reorganizing the local chromatin environment, the relative levels of NFY and YY1 binding could represent a mechanism for balancing activation and repression of Hoxb4 through the same site.

  • 34.
    Gonzalez-Castrillon, Luz Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Molecular mechanisms of nerve-tumor interactions: the intersection of cancer and neurodevelopment2023Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    A wide range of cancers throughout the body are characterized by high nerve density and invasion of cancer cells within the nerves, a process called perineural invasion (PNI). Work in the field has shown that blocking nerves in organs with tumors leads to improved disease outcomes suggesting that finding ways to block tumor nerves could lead to new treatment approaches. Despite the importance of this, little is known about the molecular mechanisms underlying nerve-tumor interactions. An increasing number of studies have revealed that the genes associated with PNI are classical neurodevelopmental genes associated with neurodevelopmental processes. Therefore, the central hypothesis of this thesis was that nerve-tumor interactions result in part from an abnormal reactivation of the molecular pathways underlying the embryonic development of the nervous system. To test this hypothesis, public datasets from different types of cancer with high incidence of PNI were analyzed to identify molecular pathways common between these cancers. This analysis revealed that neurodevelopmental pathways accounted for 12 - 16% of the differentially expressed genes (DEGs), with axon guidance genes being markedly dysregulated. Overall, 17 different axon guidance gene families, including ephrin-Eph, semaphorin-neuropilin/plexin and slit-robo pathways were dysregulated. Further disruption of these pathways was a common feature across a number of cancers analyzed and their dysregulation had a significant impact on disease survival. Overall, this suggested that neurodevelopmental molecular pathways may contribute to tumor axonogenesis and PNI. 

    These findings suggested a significant role of neurodevelopmental pathways in cancer dysregulation. Thus, a comprehensive understanding of the pathways during the nervous system development is imperative. Therefore, in my thesis, the embryo was used as a tool to study the mechanisms by which these molecular pathways influence axonogenesis more broadly. First, the role of the axon guidance genes Slit/Robo was examined during mouse neurodevelopment. Our results showed that Robo2 enrichment influences the migration and axonal projections of spinal ipsilateral neurons. In parallel, we investigated the role of alternative splicing of transcription factors as a mechanism of increase neuronal diversity. In particular we examined the expression dynamics of Lhx9, a transcription factor that controls the expression of the axon guidance gene Robo3. Lhx9 splice variants showed a differential expression at key developmental points in the spinal cord, suggesting Lhx9 splice dynamics plays an important role in neural guidance choices. 

    In the third part of the thesis, I investigated the role of gap junctions, in nerve-tumor interactions, using pancreatic ductal adenocarcinoma (PDAC) cancer cells in vitro models. The connexin GJB2 emerged as the most overexpressed gap junction component in PDAC tumors. In vitro analysis, involving blocking gap junctions or connexin overexpression, revealed that gap junctions influenced PDAC cancer cell behaviors and properties. Further we developed a novel nerve-tumor assay and used it to examine the role of gap junction genes in PDAC cells neuronal growth. 

    Overall, this thesis postulated that several key molecular pathways crucial for normal nervous system embryonic development, could underly nerve- tumor interactions during cancer development and progression.

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  • 35.
    Grebe, Markus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Plant biology: Unveiling the Casparian strip.2011Inngår i: Nature, ISSN 1476-4687, Vol. 473, nr 7347, s. 294-5Artikkel i tidsskrift (Fagfellevurdert)
  • 36.
    Gélinas-Marion, Ariane
    et al.
    School of Natural Sciences, University of Tasmania, Sandy Bay, Hobart, Australia.
    Eléouët, Morgane P.
    Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Plas Gogerddan, Aberystwyth, United Kingdom.
    Cook, Sam
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Vander Schoor, Jacqueline K.
    School of Natural Sciences, University of Tasmania, Sandy Bay, Hobart, Australia.
    Abel, Steven A. G.
    School of Natural Sciences, University of Tasmania, Sandy Bay, Hobart, Australia.
    Nichols, David S.
    Central Science Laboratory, University of Tasmania, Sandy Bay, Hobart, Australia.
    Smith, Jason A.
    School of Natural Sciences, University of Tasmania, Sandy Bay, Hobart, Australia.
    Hofer, Julie M. I.
    Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Plas Gogerddan, Aberystwyth, United Kingdom.
    Ross, John J.
    School of Natural Sciences, University of Tasmania, Sandy Bay, Hobart, Australia.
    Plant development in the garden pea as revealed by mutations in the Crd/PsYUC1 gene2023Inngår i: Genes, E-ISSN 2073-4425, Vol. 14, nr 12, artikkel-id 2115Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In common with other plant species, the garden pea (Pisum sativum) produces the auxin indole-3-acetic acid (IAA) from tryptophan via a single intermediate, indole-3-pyruvic acid (IPyA). IPyA is converted to IAA by PsYUC1, also known as Crispoid (Crd). Here, we extend our understanding of the developmental processes affected by the Crd gene by examining the phenotypic effects of crd gene mutations on leaves, flowers, and roots. We show that in pea, Crd/PsYUC1 is important for the initiation and identity of leaflets and tendrils, stamens, and lateral roots. We also report on aspects of auxin deactivation in pea.

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  • 37.
    Hanson, Johannes
    et al.
    Department of Physiological Botany, Evolutionary Biology Center, University of Uppsala.
    Regan, S.
    Engström, P.
    The expression pattern of the homeobox gene ATHB13 reveals a conservation of transcriptional regulatory mechanisms between Arabidopsis and hybrid aspen2002Inngår i: Plant Cell Reports, ISSN 0721-7714, E-ISSN 1432-203X, Vol. 21, nr 1, s. 81-89Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    ATHB13 belongs to a family of homeodomain leucine zipper (HDZip) transcription factors in Arabidopsis thaliana. To understand the temporal and spatial distribution of ATHB13 gene expression, we examined the ATHB13 promoter activity by means of fusions to the uidA (GUS, beta-glucuronidase) reporter gene in transgenic plants. The strongest promoter activity was detected in the vasculature of the basal portion of petioles for both rosette leaves and cotyledons and at the base of cauline leaves. Activity was also detected in the stem at the base of the cauline leaf in an area corresponding to the leaf gap in the vasculature. In flowers, promoter activity was also present in the receptacle and in the stigma. Transformation of the same promoter-GUS construct into hybrid aspen (Populus tremula x P. tremuloides) resulted in an analogous expression pattern in the petioles of leaves. The similarity of these expression patterns indicates that the trans-acting factors responsible for ATHB13 expression are conserved between aspen and Arabidopsis. The conserved expression pattern of the highly specific Arabidopsis ATHB13 promoter in hybrid aspen demonstrates the potential utility of Arabidopsis promoters for tissue-specific expression in angiosperm trees.

  • 38.
    Hellström, Lars
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik. School of Education, Culture and Communication, Mälardalen University, Västerås, Sweden.
    Carlsson, Linus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik. School of Education, Culture and Communication, Mälardalen University, Västerås, Sweden.
    Falster, Daniel S.
    Westoby, Mark
    Brännström, Åke
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik. Evolution and Ecology Program, International Institute for Applied Systems Analysis, Laxenburg, Austria.
    Branch Thinning and the Large-Scale, Self-Similar Structure of Trees2018Inngår i: American Naturalist, ISSN 0003-0147, E-ISSN 1537-5323, Vol. 192, nr 1, s. E37-E47Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Branch formation in trees has an inherent tendency toward exponential growth, but exponential growth in the number of branches cannot continue indefinitely. It has been suggested that trees balance this tendency toward expansion by also losing branches grown in previous growth cycles. Here, we present a model for branch formation and branch loss during ontogeny that builds on the phenomenological assumption of a branch carrying capacity. The model allows us to derive approximate analytical expressions for the number of tips on a branch, the distribution of growth modules within a branch, and the rate and size distribution of tree wood litter produced. Although limited availability of data makes empirical corroboration challenging, we show that our model can fit field observations of red maple (Acer rubrum) and note that the age distribution of discarded branches predicted by our model is qualitatively similar to an empirically observed distribution of dead and abscised branches of balsam poplar (Populus balsamifera). By showing how a simple phenomenological assumptionthat the number of branches a tree can maintain is limitedleads directly to predictions on branching structure and the rate and size distribution of branch loss, these results potentially enable more explicit modeling of woody tissues in ecosystems worldwide, with implications for the buildup of flammable fuel, nutrient cycling, and understanding of plant growth.

  • 39. Hopkins, Brian
    et al.
    Rönnqvist, Louise
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Facilitating postural control: effects on the reaching behavior of 6‐month‐old infants2002Inngår i: Developmental Psychobiology, ISSN 0012-1630, E-ISSN 1098-2302, Vol. 40, nr 2, s. 168-182Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this study, 3-D kinematic as well as 2-D videorecordings were made of the reaching behavior of infants aged about 6 months who were not yet able to sit. Detailed analyses of these recordings were directed toward specifying the effects of providing additional postural support to the lower body on the spatial and temporal features of such behavior. To detect these effects, reaching and associated head movements in this modified condition were compared to those made while the infants sat in an age-appropriate and commercially available chair lacking the supplementation of support for the pelvic region and upper legs. Findings consistent with predictions included better head stabilization and smoother reaching movements when the infants were in the modified chair. In addition, these two achievements were negatively related to reaching experience. These, and other findings, underscore the infrequently investigated supposition that changes in postural control induce improvements in the control of reaching movements during infancy. Recommendations are made about how the procedure adopted in the present study could be used in subsequent research to give further insights into the codevelopment of posture and action.

  • 40. Hopkins, Brian
    et al.
    Rönnqvist, Louise
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Human handedness: developmental, and evolutionary perspectives1998Inngår i: The development of sensory, motor and cognitive capacities in early infancy: from perception to cognition / [ed] George Butterworth and Francesca Simion, Hove, East Sussex, UK: Psychology Press, 1998, s. 191-236Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Argues (1) that handedness in humans has a greater evolutionary depth than speech and language and perhaps even habitual bipedalism, (2) that the developmental origins of handedness are based on different mechanisms than for speech and language, (3) that there is no simple task (e.g., reaching) that will provide a valid index of handedness during the 1st year, (4) that studies on the development of handedness need to be more sensitive to the roles of task and S variables, and (5) that the development of handedness should be addressed by models that incorporate hand preference into different modes of bimanual coordination. Topics discussed include: the ontology of handedness, the evolutionary origins of handedness, the developmental origins of human handedness, and the development of handedness in newborns and beyond.

  • 41. Huang, Jie
    et al.
    Liu, Ying
    Filas, Benjamen
    Gunhaga, Lena
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Beebe, David C.
    Negative and positive auto-regulation of BMP expression in early eye development2015Inngår i: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 407, nr 2, s. 256-264Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous results have shown that Bone Morphogenetic Protein (BMP) signaling is essential for lens specification and differentiation. How BMP signals are regulated in the prospective lens ectoderm is not well defined. To address this issue we have modulated BMP activity in a chicken embryo pre-lens ectoderm explant assay, and also studied transgenic mice, in which the type I BMP receptors, Bmpr1a and Acvr1, are deleted from the prospective lens ectoderm. Our results show that chicken embryo pre-lens ectoderm cells express BMPs and require BMP signaling for lens specification in vitro, and that in vivo inhibition of BMP signals in the mouse prospective lens ectoderm interrupts lens placode formation and prevents lens invagination. Furthermore, our results provide evidence that BMP expression is negatively auto-regulated in the lens-forming ectoderm, decreasing when the tissue is exposed to exogenous BMPs and increasing when BMP signaling is prevented. In addition, eyes lacking BMP receptors in the prospective lens placode develop coloboma in the adjacent wild type optic cup. In these eyes, Bmp7 expression increases in the ventral optic cup and the normal dorsal-ventral gradient of BMP signaling in the optic cup is disrupted. Pax2 becomes undetectable and expression of Sfrp2 increases in the ventral optic cup, suggesting that increased BMP signaling alter their expression, resulting in failure to close the optic fissure. In summary, our results suggest that negative and positive auto-regulation of BMP expression is important to regulate early eye development. 

  • 42.
    Hörnblad, Andreas
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM). Developmental Biology Unit, EMBL, Germany; (Epi)genomics of Animal Development Unit, Department of Developmental and Stem Cell Biology, Institut Pasteur, France; UMR3738, CNRS, Paris, France.
    Bastide, S.
    Langenfeld, K.
    Langa, F.
    Spitz, F.
    Dissection of the Fgf8 regulatory landscape by in vivo CRISPR-editing reveals extensive intra- and inter-enhancer redundancy2021Inngår i: Nature Communications, E-ISSN 2041-1723, Vol. 12, nr 1, artikkel-id 439Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Developmental genes are often regulated by multiple elements with overlapping activity. Yet, in most cases, the relative function of those elements and their contribution to endogenous gene expression remain poorly characterized. An example of this phenomenon is that distinct sets of enhancers have been proposed to direct Fgf8 in the limb apical ectodermal ridge and the midbrain-hindbrain boundary. Using in vivo CRISPR/Cas9 genome engineering, we functionally dissect this complex regulatory ensemble and demonstrate two distinct regulatory logics. In the apical ectodermal ridge, the control of Fgf8 expression appears distributed between different enhancers. In contrast, we find that in the midbrain-hindbrain boundary, one of the three active enhancers is essential while the other two are dispensable. We further dissect the essential midbrain-hindbrain boundary enhancer to reveal that it is also composed by a mixture of essential and dispensable modules. Cross-species transgenic analysis of this enhancer suggests that its composition may have changed in the vertebrate lineage.

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  • 43.
    Jansson, Stefan
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Thomas, Howard
    Senescence: developmental program or timetable?2008Inngår i: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 179, nr 3, s. 575-579Artikkel i tidsskrift (Fagfellevurdert)
  • 44.
    Jidigam, Vijay Kumar
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    BMP - a key signaling molecule in specification and morphogenesis of sensory structures2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Cranial placodes are transient thickenings of the vertebrate embryonic head ectoderm that will give rise to sensory (olfactory, lens, and otic) and non-sensory (hypophyseal) components of the peripheral nervous system (PNS). In most vertebrate embryos, these four sensory placodes undergo invagination. Epithelial invagination is a morphological process in which flat cell sheets transform into three-dimensional structures, like an epithelial pit/cup. The process of invagination is crucial during development as it plays an important role for the formation of the lens, inner ear, nasal cavity, and adenohypophysis. Using the chick as the model system the following questions were addressed. What signals are involved in placode invagination? Is there any common regulatory molecular mechanism for all sensory placode invagination, or is it controlled by unique molecular codes for each individual placode? Are placode invagination and acquisition of placode-specific identities two independent developmental processes or coupled together? To address this we used in vivo assays like electroporation and whole embryo culture. Our in vivo results provide evidence that RhoA and F-actin rearrangements, apical constriction, cell elongation and epithelial invagination are regulated by a common BMP (Bone morphogenetic protein) dependent molecular mechanism. In addition, our results show that epithelial invagination and acquisition of placode-specific identities are two independent developmental processes.

    BMP signals have been shown to be essential for lens development and patterning of the retina. However, the spatial and temporal requirement of BMP activity during early events of lens development has remained elusive. Moreover, when and how retinal cells are specified, and whether the lens plays any role for the early development of the retina is not completely known. To address these questions, we have used gain- and loss-of-function analyses in chick explant and intact embryo assays. Here, we show that during lens development BMP activity is both required and sufficient to induce the lens specific marker, L-Maf. After the L-Maf upregulation the cells are no longer dependent on BMP signaling for the next step of fiber cell differentiation, which is characterized by up-regulation of δ-crystallin expression. Regarding the specification of retinal cells our results provide evidence that at blastula stages, BMP signals inhibit the acquisition of eye-field character. Furthermore, from optic vesicle stages, BMP signals emanating from the lens are essential for maintaining eye-field identity, inhibiting telencephalic character and inducing neural retina cells.

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  • 45.
    Kahn, Tatyana G.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Savitsky, Mikhail
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Kuong, Chikuan
    Department of Computer Science, National Chengchi University, Taipei City, Taiwan.
    Jacquer, Caroline
    Institute of Human Genetics, UMR9002 CNRS, Montpellier, France.
    Cavalli, Giacomo
    Institute of Human Genetics, UMR9002 CNRS, Montpellier, France.
    Chang, Jia-Ming
    Department of Computer Science, National Chengchi University, Taipei City, Taiwan.
    Schwartz, Yuri B.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Topological screen identifies hundreds of Cp190- and CTCF-dependent Drosophila chromatin insulator elements2023Inngår i: Science Advances, E-ISSN 2375-2548, Vol. 9, nr 5, artikkel-id eade0090Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Drosophila insulators were the first DNA elements found to regulate gene expression by delimiting chromatin contacts. We still do not know how many of them exist and what impact they have on the Drosophila genome folding. Contrary to vertebrates, there is no evidence that fly insulators block cohesin-mediated chromatin loop extrusion. Therefore, their mechanism of action remains uncertain. To bridge these gaps, we mapped chromatin contacts in Drosophila cells lacking the key insulator proteins CTCF and Cp190. With this approach, we found hundreds of insulator elements. Their study indicates that Drosophila insulators play a minor role in the overall genome folding but affect chromatin contacts locally at many loci. Our observations argue that Cp190 promotes cobinding of other insulator proteins and that the model, where Drosophila insulators block chromatin contacts by forming loops, needs revision. Our insulator catalog provides an important resource to study mechanisms of genome folding.

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  • 46.
    Kolterud, Åsa
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    The Role of Lhx2 During Organogenesis: - Analysis of the Hepatic, Hematopoietic and Olfactory Systems2004Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    During embryonic development a variety of tissues and organs such as the lung, eye, and kidney are being formed. The generation of functional organs is regulated by reciprocal cell-cell interactions. Via the secretion of soluble molecules one type of cells affect the fate of their neighboring cells. A central issue in organogenesis is how a cell interprets such extrinsic signals and adopts a specific fate, and how the cell in response to this signal establishes reciprocal signaling. Transcription factors play a critical role in this process and my thesis focuses on the role of the LIM-homeodomain transcription factor, Lhx2, in the development of three different organ systems, the liver, the hematopoietic system and the olfactory system.

    The liver is formed from endoderm of the ventral foregut and mesenchyme of the septum transversum (st) and its development depends upon signaling interactions between these two tissues. As the liver becomes a distinct organ it is colonized by hematopoietic cells and serves as hematopoietic organ until birth. The fetal liver provides a microenvironment that supports the expansion of the entire hematopoietic system (HS) including the hematopoietic stem cells (HSCs). Liver development in Lhx2-/- embryos is disrupted leading to a lethal anemia due to insufficient support of hematopoiesis. To further investigate the role of Lhx2 in liver development I analyzed gene expression from the Lhx2 locus during liver development in wild-type and Lhx2-/- mice. Lhx2 is expressed in the liver associated st mesenchymal cells that become integrated in the liver and contribute to a subpopulation of hepatic stellate cells in adult liver. Lhx2 is not required for the formation of these mesenchymal cells, suggesting that the phenotype in Lhx2-/- livers is due to the presence of defective mesenchymal cells. The putative role of Lhx2 in the expansion of the HS was examined by introducing Lhx2 cDNA into embryonic stem cells differentiated in vitro. This approach allowed for the generation of immortalized multipotent hematopoietic progenitor cell (HPC) lines that share many characteristics with normal HSCs. The Lhx2-dependent generation of HSC-like cell lines suggests that Lhx2 plays a role in the maintenance and/or expansion of the HS. To isolate genes putatively linked to Lhx2 function, genes differentially expressed in the HPC lines were isolated using a cDNA subtraction approach. This allowed for the identification of a few genes putatively linked to Lhx2 function, as well as several stem cell-specific genes. The antagonist of Wnt signalling, Dickkopf-1 (Dkk-1), was identified in the former group of genes as it showed a similar expression pattern in the fetal liver, as that of Lhx2 and expression of Dkk-1 in fetal liver and in HPC lines appeared to be regulated by Lhx2. This suggests that Dkk-1 plays a role in liver development and/or HSC physiology during embryonic development.

    During development of the olfactory epithelium (OE) neuronal progenitors differentiate into mature olfactory sensory neurons (OSNs) that are individually specified into over a thousand different subpopulations, each expressing a unique odorant receptor (OR) gene. The expression of Lhx2 in olfactory neurons suggested a potential role for Lhx2 in the development of OSNs. To address this OE from Lhx2-/- and wild-type mice was compared. In the absence of functional Lhx2 neuronal differentiation was arrested prior to onset of OR expression. Lhx2 is thus required for the development of OSN progenitors into functional, individually specified OSNs.

    Thus, Lhx2 trigger a variety of cellular responses in different organ systems that play important roles in organ development in vivo and stem cell expansion in vitro.

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  • 47.
    Kolterud, Åsa
    et al.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Alenius, Mattias
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Carlsson, Leif
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Bohm, Staffan
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    The Lim homeobox gene Lhx2 is required for olfactory sensory neuron identity2004Inngår i: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 131, nr 21, s. 5319-5326Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Progenitor cells in the mouse olfactory epithelium generate over a thousand subpopulations of neurons, each expressing a unique odorant receptor (OR) gene. This event is under the control of spatial cues, since neurons in different epithelial regions are restricted to express region-specific subsets of OR genes. We show that progenitors and neurons express the LIM-homeobox gene Lhx2 and that neurons in Lhx2-null mutant embryos do not diversify into subpopulations expressing different OR genes and other region-restricted genes such as Nqo1 and Ncam2. Lhx2-/- embryos have, however, a normal distribution of Mash1-positive and neurogenin 1-positive neuronal progenitors that leave the cell cycle, acquire pan-neuronal traits and form axon bundles. Increased cell death in combination with increased expression of the early differentiation marker Neurod1, as well as reduced expression of late differentiation markers (Galphaolf and Omp), suggests that neuronal differentiation in the absence of Lhx2 is primarily inhibited at, or immediate prior to, onset of OR expression. Aberrant regional expression of early and late differentiation markers, taken together with unaltered region-restricted expression of the Msx1 homeobox gene in the progenitor cell layer of Lhx2-/- embryos, shows that Lhx2 function is not required for all aspects of regional specification of progenitors and neurons. Thus, these results indicate that a cell-autonomous function of Lhx2 is required for differentiation of progenitors into a heterogeneous population of individually and regionally specified mature olfactory sensory neurons.

  • 48.
    Kremnev, Dmitry
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Get in tune: chloroplast and nucleus harmony2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Photosynthetic eukaryots emerged as a result of several billion years of evolution between proeukaryotic cell and ancestral cyanobacteria that formed modern chloroplasts. The symbiotic relationship led to significant rearrangements in the genomes of the plastid and the nucleus: as many as 90 % of all the plastid genes were transferred to the nucleus. The gene transfer has been accompanied by the development of sophisticated regulatory signaling networks originating in the organelle (retrograde) and in the nucleus (anterograde) that coordinate development of the plastid and ensure adequate cell responses to stress signals. In this thesis I have demonstrated that transcriptional activity of PEP in the chloroplast is essential for proper embryo and seedling development in Arabidopsis thaliana. The function of PEP is dependent on the nuclear encoded PEPassociated factor PRIN2 that is able to sense the redox status of the plastid during seedling development and different stress. In response to the plastid status PRIN2 modulates the transcription activity of the PEP enzyme complex. We further established that PRIN2, as an essential component for full PEP activity, is also required to emit the Plastid Gene Expression (PGE) retrograde signal to regulate the Photosynthesis-Associated Nuclear Genes (PhANG) in the nucleus during early seedling growth via GUN1. On the other hand, regulation of PhANG expression during the High Light (HL) conditions requires functional PRIN2 and PEP activity but is GUN1-independent. Another retrograde signal produced by the developing chloroplast is associated with the tetrapyrrole biosynthesis pathway. We have established that accumulation of the chlorophyll intermediate MgProtoIX-ME in the crd mutant triggers repression of the PhANG expression, and this negative signal is mediated by a cytoplasmic protein complex containing the PAPP5 phosphatase. The nuclear targets that receive the tetrapyrrole mediated signal are GLK1 and GLK2 transcription factors that control the PhANG expression and the expression of the enzymes involved in the biosynthesis of chlorophyll.

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  • 49.
    Kuzhandaivel, Anujaianthi
    et al.
    Linköpings universitet, Avdelningen för cellbiologi.
    Schultz, Sebastian W.
    Linköpings universitet, Avdelningen för cellbiologi.
    Alkhori, Liza
    Linköpings universitet, Avdelningen för cellbiologi.
    Alenius, Mattias
    Linköpings universitet, Avdelningen för cellbiologi.
    Cilia-Mediated Hedgehog Signaling in Drosophila2014Inngår i: Cell Reports, E-ISSN 2211-1247, Vol. 7, nr 3, s. 672-680Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cilia mediate Hedgehog (Hh) signaling in vertebrates and Hh deregulation results in several clinical manifestations, such as obesity, cognitive disabilities, developmental malformations, and various cancers. Drosophila cells are nonciliated during development, which has led to the assumption that cilia-mediated Hh signaling is restricted to vertebrates. Here, we identify and characterize a cilia-mediated Hh pathway in Drosophila olfactory sensory neurons. We demonstrate that several fundamental key aspects of the vertebrate cilia pathway, such as ciliary localization of Smoothened and the requirement of the intraflagellar transport system, are present in Drosophila. We show that Cos2 and Fused are required for the ciliary transport of Smoothened and that cilia mediate the expression of the Hh pathway target genes. Taken together, our data demonstrate that Hh signaling in Drosophila can be mediated by two pathways and that the ciliary Hh pathway is conserved from Drosophila to vertebrates.

  • 50. Kvarnryd, Moa
    et al.
    Grabic, Roman
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Brandt, Ingvar
    Berg, Cecilia
    Early life progestin exposure causes arrested oocyte development, oviductal agenesis and sterility in adult Xenopus tropicalis frogs2011Inngår i: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 103, nr 1-2, s. 18-24Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Levonorgestrel (LNG) is a commonly used pharmaceutical progestin found in the environment. Information on the long-term toxicity of progestins following early life exposure is scant. We investigated the effects of developmental LNG exposure on sex differentiation, reproductive organ development and fertility in the model frog Xenopus tropicalis. Tadpoles were exposed to 0, 0.06 or 0.5 nM LNG via the water from hatching until metamorphosis. At metamorphosis effects on gonadal differentiation were evaluated using a subsample of frogs. Remaining animals were held unexposed for nine months, at which time reproductive organ structure, function and fertility were determined. LNG exposure severely impaired oviduct and ovary development and fertility. All adult females in the 0.5 nM group (n =10) completely lacked oviducts. They also displayed a significantly larger fraction of immature oocytes, arrested in meiotic prophase, than control females. Upon mating with unexposed males, only one of 11 LNG-exposed females laid eggs, whereas all control females did. No effects on testicular development, sperm count or male fertility were observed. At metamorphosis, no effects on sex ratio or gonadal histology were evident. The effects on ovarian and oviductal development were detected at adult age but not at metamorphosis, emphasising the importance of investigating the long-term consequences of developmental exposure. This is the first developmental reproductive toxicity study of a progestin in an aquatic vertebrate. Considering that several progestins are present in contaminated surface waters, further investigation into the sensitivity of frogs to progestins is warranted to understand the risk such compounds may pose to wild frog populations.

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