The research proposal in this fellowship application is directed toward delineating the genetic programs that drive retinal bipolar cell development in mice. This will be done by defining the genes regulated downstream of the homeobox transcription factor, Chx10, and the neurogenic basic helix-loop-helix (bHLH) transcription factor, Math3, in retinal progenitor cells. These factors are known to be important in bipolar cell fate determination, and the human CHX10 gene is mutated in a form of congenital blindness. The possibilities that (1) Chx10 and Math3 are co-expressed pre-cursors when bipolar fate determination is thought to occur, (2) Math3 acts to instruct the rod bipolar cell fate only in the context of Chx10 co-expression, and (3) Chx10 and neurogenic bHLH transcription factors cooperatively regulate genetic programs that influence rod bipolar cell development will be addressed by in situ hybridization, overexpression, loss-of-function, and cDNA microarray gene profiling experiments in vivo and in retinal explants. The greater understanding of the genetic programs regulated by Chx10 and Math3 in bipolar cell development could lead to identification of genes mutated in congenital blindness and design of strategies for production of specific neuronal cell types for future transplantation therapies to treat retinal degeneration.
| Kim, Douglas S; Matsuda, Takahiko; Cepko, Constance L (2008) A core paired-type and POU homeodomain-containing transcription factor program drives retinal bipolar cell gene expression. J Neurosci 28:7748-64 |
| Kim, Douglas S; Ross, Sarah E; Trimarchi, Jeffrey M et al. (2008) Identification of molecular markers of bipolar cells in the murine retina. J Comp Neurol 507:1795-810 |
