Requirement for math5 in the development of retinal ganglion cells

math5 is a murine orthologue of atonal, a bHLH proneural gene essential for the formation of photoreceptors and chordotonal organs in Drosophila. The expression of math5 coincides with the onset of retinal ganglion cell (RGC) differentiation. Targeted deletion of math5 blocks the initial differentia tion of 80% of RGCs and results in an increase in differentiated amacrine c ells. Furthermore, the absence of math5 abolishes the retinal expression of brn-3b and the formation of virtually all brn-3b-expressing RGCs. These re sults imply that math5 is a proneural gene essential for RGC differentiatio n and that math5 acts upstream to activate brn-3b-dependent differentiation processes in RGCs.