The following proposal is designed to examine factors responsible for the continued growth and regeneration of the zebrafish retina. Zebrafish will be used in these studies because they can be efficiently mutagenized and screened for eye-defects. Research will focus on characterizing the phenotype of one such mutant called round eye. Homozygosity for this mutation causes the disappearance of the marginal proliferative zone, the site of ongoing retinal growth in the adult. Heterozygosity for round eye appears to cause night blindness in adulthood. The nature of both the homozygous and heterozygous phenotypes will be examined to address the hypothesis that the regulatory mechanisms governing the continued growth and regeneration of the zebrafish retina are distinct from those operating during early embryogenesis. Histological, immunohistochemistry, in situ hybridization, ERG recordings will be used to discern the cell types affected by the mutation, as well as, the timing for the onset of the phenotype. Attempts will be made to clone the mutated gene and its interaction with other genes will be characterized using differential display and double mutant analysis. Comparisons will thereby be made between the neurogenesis occurring in the retina during early embryonic development, adulthood and regeneration after injury.
