285— Analysis of her4.1 in gef mutants

Zebrafish make an ideal model organism for studying the development of the retina and can help us understand and eventually create solutions for human eye diseases. The good effort (gef) mutant zebrafish have smaller eyes compared to the wild-type zebrafish embryos at 3 days post-fertilization. This is due to retinal degradation because of the lack of a functioning Chaf1b protein. The Chaf1b protein-coding region is disrupted due to the deletion of its coding intronic DNA which causes an exon to be lost. Chaf1b is important to the cell because it makes up one of the three parts of the chromosome assembly factor 1 (CAF-1). CAF-1 functions to regulate chromatin and load histones onto DNA, but cannot function without Chaf1b. While it has been hypothesized that Tp53-mediated apoptosis is responsible for the gef mutants’ small eyes, tp53-morphants and homozygous gef double mutants have been studied and the cell death seen in gef mutants is not correlated with Tp53 activity. Signaling pathway members Her4.1 and Ascl1a, promote retinal cell fate development. Histone deacetylases selectively regulate her4.1 and ascl1a mRNAs during retinal development, making these genes possible affected genes of the gef phenotype. Her4.1 was visualized in gef and wild-type zebrafish embryos via the in situ hybridization process.