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Nord, Hanna
Publications (10 of 15) Show all publications
Stål, P., Nord, H., von Hofsten, J., Holmlund, T. & Shah, F. K. (2024). Desmin gene expression is not ubiquitous in all upper airway myofibers and the pattern differs between healthy and sleep apnea subjects. European Journal of Medical Research, 29(1), Article ID 216.
Open this publication in new window or tab >>Desmin gene expression is not ubiquitous in all upper airway myofibers and the pattern differs between healthy and sleep apnea subjects
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2024 (English)In: European Journal of Medical Research, ISSN 0949-2321, E-ISSN 2047-783X, Vol. 29, no 1, article id 216Article in journal (Refereed) Published
Abstract [en]

Background: Desmin is a major cytoskeletal protein considered ubiquitous in mature muscle fibers. However, we earlier reported that a subgroup of muscle fibers in the soft palate of healthy subjects and obstructive sleep apnea patients (OSA) lacked immunoexpression for desmin. This raised the question of whether these fibers also lack messenger ribonucleic acid (mRNA) for desmin and can be considered a novel fiber phenotype. Moreover, some fibers in the OSA patients had an abnormal distribution and aggregates of desmin. Thus, the aim of the study was to investigate if these desmin protein abnormalities are also reflected in the expression of desmin mRNA in an upper airway muscle of healthy subjects and OSA patients.

Methods: Muscle biopsies from the musculus uvulae in the soft palate were obtained from ten healthy male subjects and six male patients with OSA. Overnight sleep apnea registrations were done for all participants. Immunohistochemistry, in-situ hybridization, and reverse transcription–quantitative polymerase chain reaction (RT–qPCR) techniques were used to evaluate the presence of desmin protein and its mRNA.

Results: Our findings demonstrated that a group of muscle fibers lacked expression for desmin mRNA and desmin protein in healthy individuals and OSA patients (12.0 ± 5.6% vs. 23.1 ± 10.8%, p = 0.03). A subpopulation of these fibers displayed a weak subsarcolemmal rim of desmin accompanied by a few scattered mRNA dots in the cytoplasm. The muscles of OSA patients also differed from healthy subjects by exhibiting muscle fibers with reorganized or accumulated aggregates of desmin protein (14.5 ± 6.5%). In these abnormal fibers, the density of mRNA was generally low or concentrated in specific regions. The overall quantification of desmin mRNA by RT–qPCR was significantly upregulated in OSA patients compared to healthy subjects (p = 0.01).

Conclusions: Our study shows evidence that muscle fibers in the human soft palate lack both mRNA and protein for desmin. This indicates a novel cytoskeletal structure and challenges the ubiquity of desmin in muscle fibers. Moreover, the observation of reorganized or accumulated aggregates of desmin mRNA and desmin protein in OSA patients suggests a disturbance in the transcription and translation process in the fibers of the patients.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2024
Keywords
Cytoskeleton, Desmin, mRNA, Muscle fiber injury, Obstructive sleep apnea, Snoring, Vibration
National Category
Respiratory Medicine and Allergy Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-223075 (URN)10.1186/s40001-024-01812-9 (DOI)38566246 (PubMedID)2-s2.0-85189198504 (Scopus ID)
Funder
Swedish Research Council, 2018‐02574The Kempe Foundations, JCSMK23-0001
Available from: 2024-04-18 Created: 2024-04-18 Last updated: 2024-04-18Bibliographically approved
Dennhag, N., Kahsay, A., Nissen, I., Nord, H., Chermenina, M., Liu, J., . . . Domellöf, F. P. (2024). fhl2b mediates extraocular muscle protection in zebrafish models of muscular dystrophies and its ectopic expression ameliorates affected body muscles. Nature Communications, 15(1), Article ID 1950.
Open this publication in new window or tab >>fhl2b mediates extraocular muscle protection in zebrafish models of muscular dystrophies and its ectopic expression ameliorates affected body muscles
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2024 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 15, no 1, article id 1950Article in journal (Refereed) Published
Abstract [en]

In muscular dystrophies, muscle fibers loose integrity and die, causing significant suffering and premature death. Strikingly, the extraocular muscles (EOMs) are spared, functioning well despite the disease progression. Although EOMs have been shown to differ from body musculature, the mechanisms underlying this inherent resistance to muscle dystrophies remain unknown. Here, we demonstrate important differences in gene expression as a response to muscle dystrophies between the EOMs and trunk muscles in zebrafish via transcriptomic profiling. We show that the LIM-protein Fhl2 is increased in response to the knockout of desmin, plectin and obscurin, cytoskeletal proteins whose knockout causes different muscle dystrophies, and contributes to disease protection of the EOMs. Moreover, we show that ectopic expression of fhl2b can partially rescue the muscle phenotype in the zebrafish Duchenne muscular dystrophy model sapje, significantly improving their survival. Therefore, Fhl2 is a protective agent and a candidate target gene for therapy of muscular dystrophies.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-222359 (URN)10.1038/s41467-024-46187-x (DOI)38431640 (PubMedID)2-s2.0-85186557555 (Scopus ID)
Available from: 2024-03-15 Created: 2024-03-15 Last updated: 2024-03-15Bibliographically approved
Kahsay, A., Dennhag, N., Liu, J.-X., Nord, H., Rönnbäck, H., Thorell, A. E., . . . Domellöf, F. P. (2024). Obscurin maintains myofiber identity in extraocular muscles. Investigative Ophthalmology and Visual Science, 65(2), Article ID 19.
Open this publication in new window or tab >>Obscurin maintains myofiber identity in extraocular muscles
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2024 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 65, no 2, article id 19Article in journal (Refereed) Published
Abstract [en]

Purpose: The cytoskeleton of the extraocular muscles (EOMs) is significantly different from that of other muscles. We aimed to investigate the role of obscurin, a fundamental cytoskeletal protein, in the EOMs.

Methods: The distribution of obscurin in human and zebrafish EOMs was compared using immunohistochemistry. The two obscurin genes in zebrafish, obscna and obscnb, were knocked out using CRISPR/Cas9, and the EOMs were investigated using immunohistochemistry, qPCR, and in situ hybridization. The optokinetic reflex (OKR) in five-day-old larvae and adult obscna−/−;obscnb−/− and sibling control zebrafish was analyzed. Swimming distance was recorded at the same age.

Results: The obscurin distribution pattern was similar in human and zebrafish EOMs. The proportion of slow and fast myofibers was reduced in obscna−/−;obscnb−/− zebrafish EOMs but not in trunk muscle, whereas the number of myofibers containing cardiac myosin myh7 was significantly increased in EOMs of obscurin double mutants. Loss of obscurin resulted in less OKRs in zebrafish larvae but not in adult zebrafish.

Conclusions: Obscurin expression is conserved in normal human and zebrafish EOMs. Loss of obscurin induces a myofiber type shift in the EOMs, with upregulation of cardiac myosin heavy chain, myh7, showing an adaptation strategy in EOMs. Our model will facilitate further studies in conditions related to obscurin.

Place, publisher, year, edition, pages
Association for Research in Vision and Ophthalmology, 2024
Keywords
extraocular muscles, myofiber, myosin heavy chain 7, obscurin, zebrafish
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-218165 (URN)10.1167/iovs.65.2.19 (DOI)38334702 (PubMedID)2-s2.0-85184789466 (Scopus ID)
Funder
Swedish Research Council, 2018-02401Umeå UniversityRegion VästerbottenUmeå University, FS 2.1.6-1911-22Stiftelsen Kronprinsessan Margaretas arbetsnämnd för synskadade
Note

Originally included in thesis in manuscript form. 

Available from: 2023-12-18 Created: 2023-12-18 Last updated: 2024-03-05Bibliographically approved
Nord, H., Kahsay, A., Dennhag, N., Domellöf, F. P. & von Hofsten, J. (2022). Genetic compensation between Pax3 and Pax7 in zebrafish appendicular muscle formation. Developmental Dynamics, 251(9), 1423-1438
Open this publication in new window or tab >>Genetic compensation between Pax3 and Pax7 in zebrafish appendicular muscle formation
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2022 (English)In: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 251, no 9, p. 1423-1438Article in journal (Refereed) Published
Abstract [en]

Background: Migrating muscle progenitors delaminate from the somite and subsequently form muscle tissue in distant anatomical regions such as the paired appendages, or limbs. In amniotes, this process requires a signaling cascade including the transcription factor paired box 3 (Pax3).

Results: In this study, we found that, unlike in mammals, pax3a/3b double mutant zebrafish develop near to normal appendicular muscle. By analyzing numerous mutant combinations of pax3a, pax3b and pax7a, and pax7b, we determined that there is a feedback system and a compensatory mechanism between Pax3 and Pax7 in this developmental process, even though Pax7 alone is not required for appendicular myogenesis. pax3a/3b/7a/7b quadruple mutant developed muscle-less pectoral fins.

Conclusions: We found that Pax3 and Pax7 are redundantly required during appendicular myogenesis in zebrafish, where Pax7 is able to activate the same developmental programs as Pax3 in the premigratory progenitor cells.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
appendicular myogenesis, limb development, muscle regeneration
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-187293 (URN)10.1002/dvdy.415 (DOI)000691719300001 ()34435397 (PubMedID)2-s2.0-85113911054 (Scopus ID)
Funder
Swedish Cancer SocietyUmeå University
Note

Special Issue

Available from: 2021-09-07 Created: 2021-09-07 Last updated: 2023-12-18Bibliographically approved
Dennhag, N., Liu, J.-X., Nord, H., von Hofsten, J. & Domellöf, F. P. (2020). Absence of Desmin in Myofibers of the Zebrafish Extraocular Muscles. Translational Vision Science & Technology, 9(10), Article ID 1.
Open this publication in new window or tab >>Absence of Desmin in Myofibers of the Zebrafish Extraocular Muscles
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2020 (English)In: Translational Vision Science & Technology, E-ISSN 2164-2591, Vol. 9, no 10, article id 1Article in journal (Refereed) Published
Abstract [en]

Purpose: To study the medial rectus (MR) muscle of zebrafish (Danio rerio) with respect to the pattern of distribution of desmin and its correlation to distinct types of myofibers and motor endplates.

Methods: The MRs of zebrafish were examined using confocal microscopy in whole-mount longitudinal specimens and in cross sections processed for immunohistochemistry with antibodies against desmin, myosin heavy chain isoforms, and innervation markers. Desmin patterns were correlated to major myofiber type and type of innervation. A total of 1382 myofibers in nine MR muscles were analyzed.

Results: Four distinct desmin immunolabeling patterns were found in the zebrafish MRs. Approximately a third of all slow myofibers lacked desmin, representing 8.5% of the total myofiber population. The adult zebrafish MR muscle displayed en grappe, en plaque, and multiterminal en plaque neuromuscular junctions (NMJs) with intricate patterns of desmin immunolabeling.

Conclusions: The MRs of zebrafish showed important similarities with the human extraocular muscles with regard to the pattern of desmin distribution and presence of the major types of NMJs and can be regarded as an adequate model to further study the role of desmin and the implications of heterogeneity in cytoskeletal protein composition.

Translational Relevance: The establishment of a zebrafish model to study the cytoskeleton in muscles that are particularly resistant to muscle disease opens new avenues to understand human myopathies and muscle dystrophies and may provide clues to new therapies.

Place, publisher, year, edition, pages
Association for Research in Vision and Ophthalmology, 2020
Keywords
extraocular muscles, desmin, neuromuscular junction, myosin heavy chain, zebrafish, multiterminal en plaque endplates
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-177160 (URN)10.1167/tvst.9.10.1 (DOI)000587388500001 ()32953241 (PubMedID)2-s2.0-85093896190 (Scopus ID)
Available from: 2020-12-08 Created: 2020-12-08 Last updated: 2023-12-18Bibliographically approved
Nord, H., Dennhag, N., Tydinger, H. & von Hofsten, J. (2019). The zebrafish HGF receptor met controls migration of myogenic progenitor cells in appendicular development. PLOS ONE, 14(7), Article ID e0219259.
Open this publication in new window or tab >>The zebrafish HGF receptor met controls migration of myogenic progenitor cells in appendicular development
2019 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 7, article id e0219259Article in journal (Refereed) Published
Abstract [en]

The hepatocyte growth factor receptor C-met plays an important role in cellular migration, which is crucial for many developmental processes as well as for cancer cell metastasis. Cmet has been linked to the development of mammalian appendicular muscle, which are derived from migrating muscle progenitor cells (MMPs) from within the somite. Mammalian limbs are homologous to the teleost pectoral and pelvic fins. In this study we used Crispr/Cas9 to mutate the zebrafish met gene and found that the MMP derived musculature of the paired appendages was severely affected. The mutation resulted in a reduced muscle fibre number, in particular in the pectoral abductor, and in a disturbed pectoral fin function. Other MMP derived muscles, such as the sternohyoid muscle and posterior hypaxial muscle were also affected in met mutants. This indicates that the role of met in MMP function and appendicular myogenesis is conserved within vertebrates.

Place, publisher, year, edition, pages
Public Library of Science, 2019
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-163701 (URN)10.1371/journal.pone.0219259 (DOI)000482328300014 ()31287821 (PubMedID)2-s2.0-85069303028 (Scopus ID)
Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2023-03-24Bibliographically approved
Nord, H., Dennhag, N., Muck, J. & von Hofsten, J. (2016). Pax7 is required for establishment of the xanthophore lineage in zebrafish embryos. Molecular Biology of the Cell, 27(11), 1853-1862
Open this publication in new window or tab >>Pax7 is required for establishment of the xanthophore lineage in zebrafish embryos
2016 (English)In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 27, no 11, p. 1853-1862Article in journal (Refereed) Published
Abstract [en]

The pigment pattern of many animal species is a result of the arrangement of different types of pigment-producing chromatophores. The zebrafish has three different types of chromatophores: black melanophores, yellow xanthophores, and shimmering iridophores arranged in a characteristic pattern of golden and blue horizontal stripes. In the zebrafish embryo, chromatophores derive from the neural crest cells. Using pax7a and pax7b zebrafish mutants, we identified a previously unknown requirement for Pax7 in xanthophore lineage formation. The absence of Pax7 results in a severe reduction of xanthophore precursor cells and a complete depletion of differentiated xanthophores in embryos as well as in adult zebrafish. In contrast, the melanophore lineage is increased in pax7a/pax7b double-mutant embryos and larvae, whereas juvenile and adult pax7a/pax7b double-mutant zebrafish display a severe decrease in melanophores and a pigment pattern disorganization indicative of a xanthophore-deficient phenotype. In summary, we propose a novel role for Pax7 in the early specification of chromatophore precursor cells.

National Category
Cell Biology Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-122559 (URN)10.1091/mbc.E15-12-0821 (DOI)000376777600015 ()27053658 (PubMedID)2-s2.0-84971261576 (Scopus ID)
Available from: 2016-06-22 Created: 2016-06-20 Last updated: 2023-03-24Bibliographically approved
Domellöf, F. P., Parkkonen, K., Lindström, M., Nord, H., von Hoffsten, J. & Li, Z. (2015). Desmin in extraocular muscles. Paper presented at Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), MAY 03-07, 2015, Denver, CO. Investigative Ophthalmology and Visual Science, 56(7)
Open this publication in new window or tab >>Desmin in extraocular muscles
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2015 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 7Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
ASSOC RESEARCH VISION OPHTHALMOLOGY, 2015
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-111515 (URN)000362882201317 ()
Conference
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), MAY 03-07, 2015, Denver, CO
Available from: 2015-11-24 Created: 2015-11-13 Last updated: 2018-06-07Bibliographically approved
Nord, H., Burguiere, A.-C., Muck, J., Nord, C., Ahlgren, U. & von Hofsten, J. (2014). Differential regulation of myosin heavy chains defines new muscle domains in zebrafish. Molecular Biology of the Cell, 25(8), 1384-1395
Open this publication in new window or tab >>Differential regulation of myosin heavy chains defines new muscle domains in zebrafish
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2014 (English)In: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 25, no 8, p. 1384-1395Article in journal (Refereed) Published
Abstract [en]

Numerous muscle lineages are formed during myogenesis within both slow-and fast-specific cell groups. In this study, we show that six fast muscle-specific myosin heavy chain genes have unique expression patterns in the zebrafish embryo. The expression of tail-specific myosin heavy chain (fmyhc2.1) requires wnt signaling and is essential for fast muscle organization within the tail. Retinoic acid treatment results in reduced wnt signaling, which leads to loss of the fmyhc2.1 domain. Retinoic acid treatment also results in a shift of muscle identity within two trunk domains defined by expression of fmyhc1.2 and fmyhc1.3 in favor of the anteriormost myosin isoform, fmyhc1.2. In summary, we identify new muscle domains along the anteroposterior axis in the zebrafish that are defined by individual nonoverlapping, differentially regulated expression of myosin heavy chain isoforms.

Place, publisher, year, edition, pages
American Society for Cell Biology, 2014
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-92681 (URN)10.1091/mbc.E13-08-0486 (DOI)000339649400017 ()24523292 (PubMedID)2-s2.0-84923040572 (Scopus ID)
Available from: 2014-09-01 Created: 2014-09-01 Last updated: 2023-03-24Bibliographically approved
Nord, H. (2014). The role of Six1 in muscle progenitor cells and the establishment of fast-twitch muscle fibres. (Doctoral dissertation). Umeå: Umeå Universitet
Open this publication in new window or tab >>The role of Six1 in muscle progenitor cells and the establishment of fast-twitch muscle fibres
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Myogenesis is the process of skeletal muscle tissue formation where committed muscle progenitor cells differentiate into skeletal muscle fibres. Depending on the instructive cues the muscle progenitor cells receive they will differentiate into specific fibre types with different properties. The skeletal muscle fibres can be broadly classified as fast-twitch fibres or slow-twitch fibres, based on their contractile speed. However, subgroups of fast- and slow-twitch fibres with different metabolic properties, endurance and different isoforms of sarcomeric components have also been identified, adding complexity to the process of muscle tissue patterning. The skeletal muscle tissue has the capacity to regenerate throughout life. Upon muscle tissue damage muscle satellite cells are recruited to the area of injury where they proliferate and either form new fibres similar to those damaged, or fuse with existing fibres.

This thesis aims to investigate the process of muscle progenitor cell proliferation and differentiation, as well as the fast-twitch fibre formation and muscle tissue patterning in the zebrafish embryo.

I present results identifying the previously uncharacterised gene myl1, encoding an alkali-like myosin light chain, which is specifically expressed in fast-twitch muscle progenitors before fibre formation. Furthermore, I introduce data showing that the transcription factor six1 is expressed in Pax7+ muscle progenitor cells, which has been reported to contribute to part of the fast-twitch muscle tissue as well as to a pool of quiescent muscle satellite cells. With support from the presented data, I hypothesise that six1 keeps the Pax7+ muscle progenitor cells in a proliferative state and consequently prevents them from differentiating into muscle fibres. In addition, I demonstrate that the zebrafish fast-twitch muscle fibres can be divided into different subgroups that express unique forms of fast myosin heavy chain genes along the anterior-posterior (head-tail) axis, and that this subspecification depends on a balance between RA and Wnt signalling.

Collectively I propose a previously unknown role for Six1 in zebrafish Pax7+ muscle progenitor cell proliferation and differentiation. Furthermore, I present novel data suggesting that distinct regions of the zebrafish body musculature are composed of different fast-twitch fibre types, and that this regionalisation is conserved in adult zebrafish.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2014. p. 47
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1684
Keywords
Myogenesis, zebrafish, muscle fibre, patterning, fmyhc, myl1, Six1, Pax7
National Category
Basic Medicine
Identifiers
urn:nbn:se:umu:diva-95849 (URN)978-91-7601-161-4 (ISBN)
Public defence
2014-12-05, Hörsal B, Unod T9, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2014-11-14 Created: 2014-11-06 Last updated: 2018-06-07Bibliographically approved
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