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Temporal Requirement of Mab21l2 During Eye Development in Chick Reveals Stage-Dependent Functions for Retinogenesis
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
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. Vol. 59, no 10, p. 3869-3878
Keywords [en]
chick, Mab21l2, development, eye, anophthalmia, coloboma, retinogenesis
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-151060DOI: 10.1167/iovs.18-24236ISI: 000441273800011PubMedID: 30073347Scopus ID: 2-s2.0-85051174142OAI: oai:DiVA.org:umu-151060DiVA, id: diva2:1245159
Available from: 2018-09-04 Created: 2018-09-04 Last updated: 2018-09-04Bibliographically approved

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Sghari, SoufienGunhaga, Lena

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