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Gunhaga, Lena
Publications (10 of 31) Show all publications
Karthikeyan, R., Davies, W. I. L. & Gunhaga, L. (2023). Non-image-forming functional roles of OPN3, OPN4 and OPN5 photopigments. Journal of Photochemistry and Photobiology, 15, Article ID 100177.
Open this publication in new window or tab >>Non-image-forming functional roles of OPN3, OPN4 and OPN5 photopigments
2023 (English)In: Journal of Photochemistry and Photobiology, E-ISSN 2666-4690, Vol. 15, article id 100177Article in journal (Refereed) Published
Abstract [en]

Detecting different wavelengths and intensities of environmental light is crucial for the survival of many animals. In response, a multiplicity of opsins (a special group of photosensitive G protein-coupled receptors), when combined with a retinal chromophore, is able to directly detect light and initiate different downstream phototransduction signaling cascades. Although avian studies from the 1930s suggested the presence of deep brain photoreceptors that could respond to seasonal changes in the light/dark cycle, it was only a few decades ago that photopigments other than those found in the visual system (i.e. rods and cones) were identified as functional photoreceptors. It is now established that several classes of non-visual photoreceptors and the photopigments they express, in lower vertebrates to higher mammals alike, can regulate a plethora of mechanisms that function outside of vision. These include the synchronization of light/dark cycles with biological/cellular rhythms of the body (i.e. photoentrainment); melanogenesis in dermal tissues; thermoregulation in adipose tissue; embryonic eye development; smooth muscle relaxation; and the development of certain cancers. These and other mechanisms have been shown, in part at least, to be controlled by the expression of three important non-visual opsin genes, namely OPN3, OPN4 and OPN5, although other vertebrate opsin classes exist, many with unknown or unclear functional roles assigned to them presently. Specifically, these three opsins have been shown to be expressed during early embryogenesis and throughout adulthood, which will be discussed here. Moreover, this review highlights recent studies that focus on several key non-image-forming functional roles of OPN3, OPN4 and OPN5, and in particular those that impact photoreception in developing structures and pathways, as well as in adulthood.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Encephalopsin, Melanopsin, Neuropsin, OPN3, OPN4, OPN5
National Category
Zoology
Identifiers
urn:nbn:se:umu:diva-206767 (URN)10.1016/j.jpap.2023.100177 (DOI)2-s2.0-85151749996 (Scopus ID)
Funder
Swedish Research Council, 2017-01430The Kempe Foundations, JCK22-0014The Kempe Foundations, SMK-1763Swedish Energy Agency, P2022-00284Kronprinsessan Margaretas Minnesfond
Available from: 2023-04-27 Created: 2023-04-27 Last updated: 2023-04-27Bibliographically approved
Panaliappan, T. K., Slekiene, L. & Gunhaga, L. (2022). CAM-Delam Assay to Score Metastatic Properties by Quantifying Delamination and Invasion Capacity of Cancer Cells. Journal of Visualized Experiments, 2022(184), Article ID e64025.
Open this publication in new window or tab >>CAM-Delam Assay to Score Metastatic Properties by Quantifying Delamination and Invasion Capacity of Cancer Cells
2022 (English)In: Journal of Visualized Experiments, E-ISSN 1940-087X, Vol. 2022, no 184, article id e64025Article in journal (Refereed) Published
Abstract [en]

The major cause of cancer-related deaths is metastasis formation (i.e., when cancer cells spread from the primary tumor to distant organs and form secondary tumors). Delamination, defined as the degradation of the basal lamina and basement membrane, is the initial process that facilitates the transmigration and spread of cancer cells to other tissues and organs. Scoring the delamination capacity of cancer cells would indicate the metastatic potential of these cells. We have developed a standardized method, the ex ovo CAM-Delam assay, to visualize and quantify the ability of cancer cells to delaminate and invade, thereby being able to assess metastatic aggressiveness. Briefly, the CAM-Delam method includes seeding cancer cells in silicone rings on the chick chorioallantoic membrane (CAM) at embryonic day 10, followed by incubation from hours to a few days. The CAM-Delam assay includes the use of an internal humidified chamber during chick embryo incubation. This novel approach increased embryo survival from 10%-50% to 80%-90%, which resolved previous technical problems with low embryo survival rates in different CAM assays. Next, the CAM samples with associated cancer cell clusters were isolated, fixed, and frozen. Finally, cryostat-sectioned samples were visualized and analyzed for basement membrane damage and cancer cell invasion using immunohistochemistry. By evaluating various known metastatic and non-metastatic cancer cell lines designed to express green fluorescent protein (GFP), the CAM-Delam quantitative results showed that the delamination capacity patterns reflect metastatic aggressiveness and can be scored into four categories. Future use of this assay, apart from quantifying delamination capacity as an indication of metastatic aggressiveness, is to unravel the molecular mechanisms that control delamination, invasion, the formation of micrometastases, and changes in the tumor microenvironment.

Place, publisher, year, edition, pages
MyJove Corporation, 2022
National Category
Cell and Molecular Biology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-203195 (URN)10.3791/64025 (DOI)000898056900081 ()35723486 (PubMedID)2-s2.0-85132454671 (Scopus ID)
Funder
Swedish Cancer Society, 18 0463Swedish Research Council, 2017-01430
Available from: 2023-01-18 Created: 2023-01-18 Last updated: 2024-01-17
Wang, T., Sarwar, M., Whitchurch, J. B., Collins, H. M., Green, T., Semenas, J., . . . Persson, J. L. (2022). PIP5K1α is Required for Promoting Tumor Progression in Castration-Resistant Prostate Cancer. Frontiers in Cell and Developmental Biology, 10, Article ID 798590.
Open this publication in new window or tab >>PIP5K1α is Required for Promoting Tumor Progression in Castration-Resistant Prostate Cancer
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2022 (English)In: Frontiers in Cell and Developmental Biology, E-ISSN 2296-634X, Vol. 10, article id 798590Article in journal (Refereed) Published
Abstract [en]

PIP5K1α has emerged as a promising drug target for the treatment of castration-resistant prostate cancer (CRPC), as it acts upstream of the PI3K/AKT signaling pathway to promote prostate cancer (PCa) growth, survival and invasion. However, little is known of the molecular actions of PIP5K1α in this process. Here, we show that siRNA-mediated knockdown of PIP5K1α and blockade of PIP5K1α action using its small molecule inhibitor ISA-2011B suppress growth and invasion of CRPC cells. We demonstrate that targeted deletion of the N-terminal domain of PIP5K1α in CRPC cells results in reduced growth and migratory ability of cancer cells. Further, the xenograft tumors lacking the N-terminal domain of PIP5K1α exhibited reduced tumor growth and aggressiveness in xenograft mice as compared to that of controls. The N-terminal domain of PIP5K1α is required for regulation of mRNA expression and protein stability of PIP5K1α. This suggests that the expression and oncogenic activity of PIP5K1α are in part dependent on its N-terminal domain. We further show that PIP5K1α acts as an upstream regulator of the androgen receptor (AR) and AR target genes including CDK1 and MMP9 that are key factors promoting growth, survival and invasion of PCa cells. ISA-2011B exhibited a significant inhibitory effect on AR target genes including CDK1 and MMP9 in CRPC cells with wild-type PIP5K1α and in CRPC cells lacking the N-terminal domain of PIP5K1α. These results indicate that the growth of PIP5K1α-dependent tumors is in part dependent on the integrity of the N-terminal sequence of this kinase. Our study identifies a novel functional mechanism involving PIP5K1α, confirming that PIP5K1α is an intriguing target for cancer treatment, especially for treatment of CRPC.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2022
Keywords
androgen receptor (AR), castration-resistant prostate cancer (CRPC), cyclin-dependent kinase (CDK), matrix metalloproteinases 9 (MMP9) PIP5K1α, phosphatidylinositol 4-phosphate 5 kinase (PIP5K1α), targeted therapy
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-193614 (URN)10.3389/fcell.2022.798590 (DOI)000780059400001 ()35386201 (PubMedID)2-s2.0-85128078251 (Scopus ID)
Funder
EU, Horizon 2020, 721297Swedish Childhood Cancer Foundation, TJ2015-0097Swedish Cancer Society, CAN-2017-381Swedish Research Council, 2019-01318The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IG2013-5595The Kempe FoundationsCancerforskningsfonden i Norrland
Available from: 2022-04-07 Created: 2022-04-07 Last updated: 2023-05-23Bibliographically approved
Dakhel, S., Davies, W. I. L., Joseph, J. V., Tomar, T., Remeseiro, S. & Gunhaga, L. (2021). Chick fetal organ spheroids as a model to study development and disease. BMC Molecular and Cell Biology, 22(1), Article ID 37.
Open this publication in new window or tab >>Chick fetal organ spheroids as a model to study development and disease
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2021 (English)In: BMC Molecular and Cell Biology, E-ISSN 2661-8850, Vol. 22, no 1, article id 37Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Organ culture models have been used over the past few decades to study development and disease. The in vitro three-dimensional (3D) culture system of organoids is well known, however, these 3D systems are both costly and difficult to culture and maintain. As such, less expensive, faster and less complex methods to maintain 3D cell culture models would complement the use of organoids. Chick embryos have been used as a model to study human biology for centuries, with many fundamental discoveries as a result. These include cell type induction, cell competence, plasticity and contact inhibition, which indicates the relevance of using chick embryos when studying developmental biology and disease mechanisms.

RESULTS: Here, we present an updated protocol that enables time efficient, cost effective and long-term expansion of fetal organ spheroids (FOSs) from chick embryos. Utilizing this protocol, we generated FOSs in an anchorage-independent growth pattern from seven different organs, including brain, lung, heart, liver, stomach, intestine and epidermis. These three-dimensional (3D) structures recapitulate many cellular and structural aspects of their in vivo counterpart organs and serve as a useful developmental model. In addition, we show a functional application of FOSs to analyze cell-cell interaction and cell invasion patterns as observed in cancer.

CONCLUSION: The establishment of a broad ranging and highly effective method to generate FOSs from different organs was successful in terms of the formation of healthy, proliferating 3D organ spheroids that exhibited organ-like characteristics. Potential applications of chick FOSs are their use in studies of cell-to-cell contact, cell fusion and tumor invasion under defined conditions. Future studies will reveal whether chick FOSs also can be applicable in scientific areas such as viral infections, drug screening, cancer diagnostics and/or tissue engineering.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2021
Keywords
3D cell culture, Cancer, Chick, Development, Fetal organ spheroids, Invasion
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-186439 (URN)10.1186/s12860-021-00374-6 (DOI)000669871300001 ()34225662 (PubMedID)2-s2.0-85110859058 (Scopus ID)
Funder
Swedish Cancer Society, 18 0463Cancerforskningsfonden i Norrland
Available from: 2021-08-02 Created: 2021-08-02 Last updated: 2023-10-05Bibliographically approved
Davies, W. I. L., Sghari, S., Upton, B. A., Nord, C., Hahn, M., Ahlgren, U., . . . Gunhaga, L. (2021). Distinct opsin 3 (Opn3) expression in the developing nervous system during mammalian embryogenesis. eNeuro, 8(5), Article ID ENEURO.0141-21.2021.
Open this publication in new window or tab >>Distinct opsin 3 (Opn3) expression in the developing nervous system during mammalian embryogenesis
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2021 (English)In: eNeuro, E-ISSN 2373-2822, Vol. 8, no 5, article id ENEURO.0141-21.2021Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Society for Neuroscience, 2021
Keywords
Brain, Development, Encephalopsin, Nervous system, Opn3, OPT
National Category
Neurosciences Developmental Biology
Identifiers
urn:nbn:se:umu:diva-187852 (URN)10.1523/ENEURO.0141-21.2021 (DOI)000704430100013 ()34417283 (PubMedID)2-s2.0-85114912713 (Scopus ID)
Funder
Swedish Research Council, 2017-01430The Kempe Foundations, SMK-1763Swedish Research Council, 2017-01307
Available from: 2021-09-23 Created: 2021-09-23 Last updated: 2023-09-05Bibliographically approved
Panaliappan, T. K., Slekiene, L., Jonasson, A.-K., Gilthorpe, J. D. & Gunhaga, L. (2020). CAM-Delam: an in vivo approach to visualize and quantify the delamination and invasion capacity of human cancer cells. Scientific Reports, 10(1), Article ID 10472.
Open this publication in new window or tab >>CAM-Delam: an in vivo approach to visualize and quantify the delamination and invasion capacity of human cancer cells
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2020 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 10472Article in journal (Refereed) Published
Abstract [en]

The development of metastases is the major cause of cancer related death. To develop a standardized method that define the ability of human cancer cells to degrade the basement membrane, e.g. the delamination capacity, is of importance to assess metastatic aggressiveness. We now present the in vivo CAM-Delam assay to visualize and quantify the ability of human cancer cells to delaminate and invade. The method includes seeding cancer cells on the chick chorioallantoic membrane (CAM), followed by the evaluation of cancer-induced delamination and potential invasion within hours to a few days. By testing a range of human cancer cell lines in the CAM-Delam assay, our results show that the delamination capacity can be divided into four categories and used to quantify metastatic aggressiveness. Our results emphasize the usefulness of this assay for quantifying delamination capacity as a measurement of metastatic aggressiveness, and in unraveling the molecular mechanisms that regulate delamination, invasion, formation of micro-metastases and modulations of the tumor microenvironment. This method will be useful in both the preclinical and clinical characterization of tumor biopsies, and in the validation of compounds that may improve survival in metastatic cancer.

Place, publisher, year, edition, pages
Nature Publishing Group, 2020
National Category
Cancer and Oncology
Research subject
Biological Research on Drug Dependence; Oncology
Identifiers
urn:nbn:se:umu:diva-173655 (URN)10.1038/s41598-020-67492-7 (DOI)000545967200069 ()32591581 (PubMedID)2-s2.0-85086871538 (Scopus ID)
Funder
Swedish Cancer Society, A549Swedish Cancer Society, SW620Swedish Cancer Society, 143BSwedish Cancer Society, 18 0463Cancerforskningsfonden i NorrlandSwedish Research Council, 2017-01430Knut and Alice Wallenberg Foundation, KAW2012.0091
Available from: 2020-07-21 Created: 2020-07-21 Last updated: 2024-04-10Bibliographically approved
Sghari, S., Davies, W. I. L. & Gunhaga, L. (2020). Elucidation of Cellular Mechanisms That Regulate the Sustained Contraction and Relaxation of the Mammalian Iris. Investigative Ophthalmology and Visual Science, 61(11), Article ID 5.
Open this publication in new window or tab >>Elucidation of Cellular Mechanisms That Regulate the Sustained Contraction and Relaxation of the Mammalian Iris
2020 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 61, no 11, article id 5Article in journal (Refereed) Published
Abstract [en]

PURPOSE. In mammals, pupil constriction and dilation form the pupillary light reflex (PLR), which is mediated by both brain-regulated (parasympathetic) and local iris-driven reflexes. To better understand the cellular mechanisms that regulate pupil physiological dynamics via central and local photoreception, we have examined the regulation of the PLR via parasympathetic and local activation, respectively.

METHODS. In this study, the PLR was examined in mouse enucleated eyes ex vivo in real-time under different ionic conditions in response to acetylcholine and/or blue light (480 nm). The use of pupillometry recordings captured the relaxation, contraction, and pupil escape (redilation) processes for 10 minutes up to 1 hour.

RESULTS. Among others, our results show that ryanodine receptor channels are the main driver for iridal stimulation-contraction coupling, in which extracellular influx of Ca2+ is required for amplification of pupil constriction. Both local and parasympathetic iridal activations are necessary, but not sufficient for sustained pupil constriction. Moreover, the degree of membrane potential repolarization in the dark is correlated with the latency and velocity of iridal constriction. Furthermore, pupil escape is driven by membrane potential hyperpolarization where voltage-gated potassium channels play a crucial role.

CONCLUSIONS. Together, this study presents new mechanisms regulating synchronized pupil dilation and contraction, sustained pupil constriction, iridal stimulation-contraction coupling, and pupil escape.

Place, publisher, year, edition, pages
Rockville: Association of Research in Vision and Ophthalmology, 2020
Keywords
iris, pupil light reflex, acetylcholine, melanopsin, mouse
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-176061 (URN)10.1167/iovs.61.11.5 (DOI)000574650900040 ()32882011 (PubMedID)2-s2.0-85090320546 (Scopus ID)
Available from: 2020-11-06 Created: 2020-11-06 Last updated: 2023-03-24Bibliographically approved
Panaliappan, T. K., Slekiene, L., Gunhaga, L. & Patthey, C. (2019). Extensive apoptosis during the formation of the terminal nerve ganglion by olfactory placode-derived cells with distinct molecular markers. Differentiation, 110, 8-16
Open this publication in new window or tab >>Extensive apoptosis during the formation of the terminal nerve ganglion by olfactory placode-derived cells with distinct molecular markers
2019 (English)In: Differentiation, ISSN 0301-4681, E-ISSN 1432-0436, Vol. 110, p. 8-16Article in journal (Refereed) Published
Abstract [en]

The terminal nerve ganglion (TNG) is a well-known structure of the peripheral nervous system in cartilaginous and teleost fishes. It derives from the olfactory placode during embryonic development. While the differentiation and migration of gonadotropin releasing hormone (GnRH)-expressing neurons from the olfactory placode has been well documented, the TNG has been neglected in birds and mammals, and its development is less well described. Here we describe the formation of a ganglion-like structure from migratory olfactory placodal cells in chicken. The TNG is surrounded by neural crest cells, but in contrast to other cranial sensory ganglia, we observed no neural crest corridor, and olfactory unsheathing cells appear only after the onset of neuronal migration. We identified Isl1 and Lhx2 as two transcription factors that label neuronal subpopulations in the forming TNG, distinct from GnRH1(+) cells, thereby revealing a diversity of cell types during the formation of the TNG. We also provide evidence for extensive apoptosis in the terminal nerve ganglion shortly after its formation, but not in other cranial sensory ganglia. Moreover, at later stages placode-derived neurons expressing GnRH1, Isl1 and/or Lhx2 become incorporated in the telencephalon. The integration of TNG neurons into the telencephalon together with the earlier widespread apoptosis in the TNG might be an explanation why the TNG in mammals and birds is much smaller compared to other vertebrates.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Terminal nerve ganglion, Apoptosis, Lhx2, GnRH, Isl1, Chicken
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-167041 (URN)10.1016/j.diff.2019.09.003 (DOI)000498845100002 ()31539705 (PubMedID)2-s2.0-85072197946 (Scopus ID)
Funder
Swedish Research Council, 2017-01430_3
Available from: 2020-01-08 Created: 2020-01-08 Last updated: 2023-03-24Bibliographically approved
Panaliappan, T. K., Wittmann, W., Jidigam, V. K., Mercurio, S., Bertolini, J. A., Sghari, S., . . . Gunhaga, L. (2018). Sox2 is required for olfactory pit formation and olfactory neurogenesis through BMP restriction and Hes5 upregulation. Development, 145(2), Article ID dev153791.
Open this publication in new window or tab >>Sox2 is required for olfactory pit formation and olfactory neurogenesis through BMP restriction and Hes5 upregulation
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2018 (English)In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 145, no 2, article id dev153791Article in journal (Refereed) Published
Abstract [en]

The transcription factor Sox2 is necessary to maintain pluripotency of embryonic stem cells, and to regulate neural development. Neurogenesis in the vertebrate olfactory epithelium persists from embryonic stages through adulthood. The role Sox2 plays for the development of the olfactory epithelium and neurogenesis within has, however, not been determined. Here, by analysing Sox2 conditional knockout mouse embryos and chick embryos deprived of Sox2 in the olfactory epithelium using CRISPR-Cas9, we show that Sox2 activity is crucial for the induction of the neural progenitor gene Hes5 and for subsequent differentiation of the neuronal lineage. Our results also suggest that Sox2 activity promotes the neurogenic domain in the nasal epithelium by restricting Bmp4 expression. The Sox2-deficient olfactory epithelium displays diminished cell cycle progression and proliferation, a dramatic increase in apoptosis and finally olfactory pit atrophy. Moreover, chromatin immunoprecipitation data show that Sox2 directly binds to the Hes5 promoter in both the PNS and CNS. Taken together, our results indicate that Sox2 is essential to establish, maintain and expand the neuronal progenitor pool by suppressing Bmp4 and upregulating Hes5 expression.

Place, publisher, year, edition, pages
Company of Biologists Ltd, 2018
Keywords
Sox2, Hes5, Olfactory epithelium, Neurogenesis, Mouse
National Category
Developmental Biology Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-145166 (URN)10.1242/dev.153791 (DOI)000424412000009 ()2-s2.0-85041301091 (Scopus ID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2023-03-24Bibliographically approved
Sghari, S. & Gunhaga, L. (2018). Temporal Requirement of Mab21l2 During Eye Development in Chick Reveals Stage-Dependent Functions for Retinogenesis. Investigative Ophthalmology and Visual Science, 59(10), 3869-3878
Open this publication in new window or tab >>Temporal Requirement of Mab21l2 During Eye Development in Chick Reveals Stage-Dependent Functions for Retinogenesis
2018 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 10, p. 3869-3878Article in journal (Refereed) Published
Abstract [en]

Different missense mutations in the single exon gene Mab21l2 have been identified in unrelated families with various bilateral eye malformations, including microphthalmia, anophthalmia, and coloboma, but the molecular function of Mab21l2 during eye development still remains largely unknown. METHODS. We have established an in vivo Mab21l2-deficient eye development model in chick, by using a Mab21l2 RNA interference construct that we electroporated in ovo in prospective retinal cells. In addition, we designed a Mab21l2 gain-of-function electroporation vector. Mab21l2-modulated retinas were analyzed on consecutive sections in terms of morphology, and molecular markers for apoptosis, cell proliferation, and retinogenesis. RESULTS. Our Mab21l2-deficient chick model mimics human ocular phenotypes. When Mab21l2 is downregulated prior to optic vesicle formation, the embryos develop anophthalmia, and Mab21l2 inhibition by optic cup stages results in a microphthalmic colobomatous phenotype. Our results show that inhibition of Mab21l2 affects cell proliferation, cell cycle exit, and the expression of Atoh7/Ath5, NeuroD4/Ath3, Isl1, Pax6, AP-2a, and Prox1. In addition, Mab21l2 overexpression hampers cell cycle exit and differentiation of retinal progenitor cells (RPCs). CONCLUSIONS. Our results highlight the importance of a regulated temporal expression of Mab21l2 during eye development: At early stages, Mab21l2 is required to maintain RPC proliferation and expansion of cell number; before retinogenesis, a decrease in Mab21l2 expression in proliferating RPCs is required for cell cycle exit and differentiation; during retinogenesis, Mab21l2 is chronologically upregulated in RGCs, followed by differentiated horizontal and amacrine cells and cone photoreceptor cells.

Place, publisher, year, edition, pages
ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018
Keywords
chick, Mab21l2, development, eye, anophthalmia, coloboma, retinogenesis
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-151060 (URN)10.1167/iovs.18-24236 (DOI)000441273800011 ()30073347 (PubMedID)2-s2.0-85051174142 (Scopus ID)
Available from: 2018-09-04 Created: 2018-09-04 Last updated: 2018-09-04Bibliographically approved
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