The small eyes of good effort zebrafish mutant result from a splicing defect in chromosome assembly factor 1, subunit...

The differentiation of diverse retinal neurons, such as photoreceptors, is dependent on the complex interactions of cell cycle and differentiation control genes. Failure to properly regulate these interactions can lead to Tumor protein p53 (Tp53)-mediated cell death. Screening of N-ethyl N-nitrosourea-induced mutants for small eyes and meiotic mapping resulted in the identification of the good effort (gef) mutant as an allele of chromosome assembly factor 1, subunit b (chaf1b^nt2). The developmental defects in these mutants correlate with a splicing defect caused by a genomic deletion which overlaps a splice donor site of exon three of chaf1b. The differentiation defects of retinal and neural crest cells in the chaf1b^nt2 mutant match those of chaf1b^t24412 mutant zebrafish. Injection of wild-type chaf1b mRNA rescues the small-eye defect of chaf1b^nt2 mutants and morpholino targeting of chaf1b^nt2 phenocopies the mutation. Neither morpholino knockdown nor genetic disruption of tp53 decreased cell death in chaf1b^nt2 mutants indicating a possible Tp53-independent cell death pathway. Progenitor and differentiating cell gene expression profiles were altered in chaf1b^nt2 mutants compared with wild-type. These results indicate a requirement for Chaf1b function in the regulation of gene expression in the developing retina.