Faculty Collaboration Database

dazed gene is necessary for late cell type development and retinal cell maintenance in the zebrafish retina. Dev Dyn 2005 Jun;233(2):680-94

Date

04/22/2005

Pubmed ID

15844196

DOI

10.1002/dvdy.20375

Scopus ID

2-s2.0-19544370700 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

Several molecules, such as growth factors and neurotrophic factors, are required both for the differentiation of specific retinal cell types and the long-term cell survival of all retinal neurons. As diffusible factors, these molecules act non-cell-autonomously. Here, we describe the loss of function phenotype for dazed (dzd), a gene that acts cell-autonomously for retinal cell survival and affects the differentiation of rod photoreceptors and the Muller glia. By 3 days after fertilization, dazed mutant embryos have small eyes and slight heart edema. Acridine orange staining indicated a significant degree of retinal cell death occurring by 48 hr after fertilization, and histological analysis revealed that dying cells were found in the inner and outer nuclear layers and near the marginal zones. Although molecular and morphological differentiation of the inner retina and cone photoreceptors occurred, rod photoreceptors failed to differentiate beyond a small patch in the ventral retina and rod precursors failed to respond to exogenously added retinoic acid, which normally potentiated rod differentiation. Mosaic analysis indicated that the dazed gene acts cell-autonomously for rod production and cell survival, as dazed clones failed to produce rods outside the ventral patch and dazed cells were not maintained in wild-type hosts. Raising mutants under constant light resulted in severe retinal degeneration, whereas raising embryos under constant darkness did not provide any additional protection from cell death. Behavioral analysis showed that a subpopulation of adult fish that were heterozygous for the dazed mutation had elevated visual thresholds and were night blind, suggesting that dazed may also be required for long-term dim-light vision. Taken together, our studies suggest a role for the dazed gene in rod and Muller cell development and overall retinal cell survival and maintenance.

Author List

Perkins BD, Nicholas CS, Baye LM, Link BA, Dowling JE

Author

Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aging
Animals
Animals, Genetically Modified
Blindness
Cell Death
Cell Differentiation
Cell Proliferation
Cell Survival
Embryo, Nonmammalian
Eye Proteins
Gene Expression Regulation, Developmental
Heterozygote
Light
Male
Mutation
Retina
Retinal Rod Photoreceptor Cells
Time Factors
Zebrafish
Zebrafish Proteins