Cell fate determination in teleost fish retina.

Development and differentiation of the retina was studied with a focus on environmental interactions which direct cell fate. Three populations of proliferating cells with the potential to generate new neurons were studied: rod precursors, retinal germinal zone, and retinal pigmented epithelium (RPE). Rod precursor cells in the mature teleost retina continuously generate rod photoreceptors. Immunocytochemistry with antibodies against a cell proliferation marker, BrdU, and against opsin was used to determine whether rod precursors express rod opsin. We found that they do not; opsin expression begins after the terminal mitotic division. These results support the hypothesis that dividing rod precursor cells are multipotent cells not pre-determined to differentiate as rods. Because the fate of rod precursors differs from that of neuroepithelial cells in the germinal zone, we hypothesized that these two proliferating populations would differ in their expression of the adhesion molecule N-cadherin. In situ hybridization with a zebrafish N-cadherin probe (ZNcad) was combined with BrdU immunocytochemistry on developing zebrafish embryos. We found that ZNcad was expressed by all retinal cells early in embryogenesis, and was later restricted to the inner layers and the germinal zone. Rod precursors never expressed ZNcad, nor did dividing cells which gave rise to cone photoreceptors. Thus, both rod and cone precursors differed from germinal zone cells. The capacity of RPE in adult goldfish to transdifferentiate into neural retina was investigated. Retinas were pre-labeled with Fluoro-Gold to distinguish residual retina from new retina. When retinas were completely removed, no regeneration took place. When retinas were partially removed, new neurons were found within and at the cut edge of the residual retina. These new neurons were derived from rod precursors in the blastema and from within the retina, but not from RPE. This suggests that while RPE cells cannot change their fate, rod precursors can. Overall, these studies suggest that rod precursors are directed into different pathways of differentiation by changes in their environment, which may be reflected by changes in the expression of adhesion molecules. Unlike rod precursors, the RPE cells in adult goldfish are not competent to alter their fate.PhDNeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/104331/1/9513398.pdfDescription of 9513398.pdf : Restricted to UM users only