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Abnormal retinal development in Cloche mutant zebrafish
Author(s) -
Dhakal Susov,
Stevens Craig B.,
Sebbagh Meyrav,
Weiss Omri,
Frey Ruth A.,
Adamson Seth,
Shelden Eric A.,
Inbal Adi,
Stenkamp Deborah L.
Publication year - 2015
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24322
Subject(s) - biology , zebrafish , retina , muller glia , retinal , microbiology and biotechnology , eye development , neural development , embryonic stem cell , embryo , embryogenesis , cell fate determination , anatomy , phenotype , neuroscience , transcription factor , genetics , progenitor cell , stem cell , biochemistry , gene
Background: Functions for the early embryonic vasculature in regulating development of central nervous system tissues, such as the retina, have been suggested by in vitro studies and by in vivo manipulations that caused additional ocular vessels to develop. Here, we use an avascular zebrafish embryo, cloche−/− ( clo−/− ), to begin to identify necessary developmental functions of the ocular vasculature in regulating development and patterning of the neural retina, in vivo. These studies are possible in zebrafish embryos, which do not yet rely upon the vasculature for tissue oxygenation. Results: clo−/− embryos lacked early ocular vasculature and were microphthalmic, with reduced retinal cell proliferation and cell survival. Retinas of clo mutants were disorganized, with irregular synaptic layers, mispatterned expression domains of retinal transcription factors, morphologically abnormal Müller glia, reduced differentiation of specific retinal cell types, and sporadically distributed cone photoreceptors. Blockade of p53‐mediated cell death did not completely rescue this phenotype and revealed ectopic cones in the inner nuclear layer. clo−/− embryos did not upregulate a molecular marker for hypoxia. Conclusions: The disorganized retinal phenotype of clo−/− embryos is consistent with a neural and glial developmental patterning role for the early ocular vasculature that is independent of its eventual function in gas exchange. Developmental Dynamics 244:1439–1455, 2015 . © 2015 Wiley Periodicals, Inc.