Abnormal retinal development in Cloche mutant zebrafish

Susov Dhakal, Craig B. Stevens, Meyrav Sebbagh, Omri Weiss, Ruth A. Frey, Seth Adamson, Eric A. Shelden, Adi Inbal, Deborah L. Stenkamp*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageAmerican English
Pages (from-to)1439-1455
Number of pages17
JournalDevelopmental Dynamics
Issue number11
StatePublished - Nov 2015

Bibliographical note

Publisher Copyright:
© 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.


  • Müller glia
  • Neurod1
  • Neurogenesis
  • Pax6a
  • Photoreceptors
  • Retina
  • Vasculature
  • Zebrafish


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