PUBLICATION
Abnormal retinal development in cloche mutant zebrafish
- Authors
- Dhakal, S., Stevens, C.B., Sebbagh, M., Weiss, O., Frey, R.A., Adamson, S., Shelden, E.A., Inbal, A., Stenkamp, D.L.
- ID
- ZDB-PUB-150819-5
- Date
- 2015
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 244(11): 1439-55 (Journal)
- Registered Authors
- Keywords
- Müller glia, Retina, neurod1, neurogenesis, pax6a, photoreceptors, vasculature, zebrafish
- MeSH Terms
-
- Zebrafish/genetics*
- Cell Survival
- Neuroglia/physiology
- Cell Death
- Animals, Genetically Modified
- Retina/abnormalities*
- Retina/embryology*
- Cell Proliferation
- Hypoxia
- Mutation*
- Phenotype
- Microscopy, Confocal
- Animals
- Cell Differentiation
- Gene Expression Regulation, Developmental
- Stem Cells
- Neurons/physiology
- Embryo, Nonmammalian/metabolism
- Retinal Pigment Epithelium/metabolism
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/physiology
- Basic Helix-Loop-Helix Transcription Factors/genetics*
- Basic Helix-Loop-Helix Transcription Factors/physiology
- PubMed
- 26283463 Full text @ Dev. Dyn.
Citation
Dhakal, S., Stevens, C.B., Sebbagh, M., Weiss, O., Frey, R.A., Adamson, S., Shelden, E.A., Inbal, A., Stenkamp, D.L. (2015) Abnormal retinal development in cloche mutant zebrafish. Developmental Dynamics : an official publication of the American Association of Anatomists. 244(11):1439-55.
Abstract
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. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping