Math5 encodes a murine basic helix-loop-helix transcription factor expressed during early stages of retinal neurogenesis

We have identified Math5, a mouse basic helix-loop-helix (bHLH) gene that i s closely related to Drosophila atonal and Xenopus Xath5 anal is largely re stricted to the developing eye. Math5 retinal expression precedes different iation of the first neurons and persists within progenitor cells until afte r birth. To position Math5 in a hierarchy of retinal development, we compar ed Math5 and Hes1 expression in wild-type and Pax6-deficient (Sey) embryos, Math5 expression is downregulated in Sey/+ eyes and abolished in Sey/Sey e ye rudiments, whereas the bHLH gene Hes1 is upregulated in a similar dose-d ependent manner. These results link Pax6 to the process of retinal neurogen esis and provide the first molecular correlate for the dosage-sensitivity o f the Pax6 phenotype. During retinogenesis, Math5 is expressed significantl y before NeuroD, Ngn2 or Mash1, To test whether these bHLH genes influence the fates of distinct classes of retinal neurons, we ectopically expressed Math5 and Mash1 in Xenopus retinal progenitors. Unexpectedly, lipofection o f either mouse gene into the frog retina caused an increase in differentiat ed bipolar cells. Directed expression of Math5, but not Xath5, in Xenopus b lastomeres produced an expanded retinal phenotype, We propose that Math5 ac ts as a proneural gene, but has properties different from its most closely related vertebrate family member, Xath5.