Lin Gan, Ph.D.
Associate Professor of Ophthalmology and Neurobiology & Anatomy
Ph.D. 1992, University of Texas

Research: Genetic analysis of regulatory network controlling the commitment and differentiation of retinal neurons inmammalian development.

Transcriptional factors play an important role in the neuronal cell specification, differentiation, and maturation. In our earlier studies, we have shown that the targeted deletions of he close-related POU-domain genes, brn-3a, brn-3b and brn-3c, result in the loss of neurons in the somatosensory, retina and inner ear, respectively. To further investigate the mechanisms of the neuronal cell loss in these mutants, we have used the lacZ and human placental alkaline phosphatase knocked into brn-3b locus to study the fate and axonal projection process of the brn-3b mutant retinal ganglion cells in vivo and in explant culture. Our results indicated that brn-3b gene was not required for the initial commitment of neuronal progenitor cells to the retinal ganglion cell fate or for the migration of these cells to the retinal ganglion cell layer. However, brn-3b gene was imperative for the terminal differentiation of retinal ganglion cells. Without brn-3b gene, the retina ganglion cells failed to project axonal process during development and degenerated by apoptosis. Our results suggest that brn-3b gene controls the activity of genes which play essential roles in the formation of retinal ganglion cells. Similarly, we use the targeted mutation approach to study the role of mouse math5 gene, a bHLH transcriptional factor gene homologous to Drosophila atonal gene. Expression of the math5 were first detected in cells destined for the retinal ganglion cell fate and prior to the activation of brn-3b gene. The expression profile of math5 gene suggests its role in the initial commitment of retinal progenitor cells to retinal ganglion cell fate. Deletion of math5 in mouse resulted in the severe loss of retinal ganglion cells during embryonic development. Our results indicated that math5 may indeed function in determining the retinal ganglion cell fate.