The role of Prdm8 in mammalian eye development. (360G-Wellcome-084585_Z_07_Z)

Although eye development in different organisms produces dramatically different structures, like the compound eye of insects and the camera-like eye of vertebrates, the underlying molecular mechanisms are highly conserved. Animal models have proven to be highly informative of the intrinsic network of transcription factors (TFs) that regulates human eye formation, and mutations in a number of TF genes have subsequently been shown to cause inherited eye and retinal cell type-specific defects in h umans. The aim of the proposed research is to define the role of the putative TF, Prdm8, in eye development and identify its downstream target genes. Adult mice homozygous for a Prdm8 null allele (Prdm8-/-) lack the major class of retinal interneurons, rod bipolar cells. My first goal will be to define the population of genes that are differentially expressed in the developing retinas of wild-type vs. Prdm8-/- mice. My second goal will be to identify the consensus DNA-binding site for Prdm8. Those genes that are: (i) differentially expressed in Prdm8-/- vs wildtype mice, (ii) expressed in the same retinal cell types as Prdm8, and (iii) contain the Prdm8 consensus DNA-binding sequence(s), are likely to be direct downstream target genes for Prdm8, involved in retinal bipolar cell formation.