Retinal ganglion cell genesis requires lakritz, a zebrafish atonal homolog

Mutation of the zebrafish lakritz (lak) locus completely eliminates the ear liest-born retinal cells, the ganglion cells (RGCs). Instead, excess amacri ne, bipolar, and Muller glial cells are generated in the mutant. The extra amacrines are found at ectopic locations in the ganglion cell layer. Cone p hotoreceptors appear unaffected by the mutation. Molecular analysis reveals that lak encodes Ath5, the zebrafish eye-specific ortholog of the Drosophi la basic helix-loop-helix transcription factor Atonal. A combined birth-dat ing and cell marker analysis demonstrates that lak/ath5 is essential for RG C determination during the first wave of neurogenesis in the retina. Our re sults suggest that this wave is skipped in the mutant, leading to an accumu lation of progenitors for inner nuclear layer cells.