During retinal development, seven retinal cell types are specified from a common pool of retina progenitor cells (RPCs). Several proneural basic helix-loop-helix (bHLH) transcriptional regulators, including Atoh7 and Neurod1, direct the intrinsic programming of RPCs but how do individual bHLH factors influence RPC fate? On p. , William Klein and colleagues ask whether replacing one bHLH gene with another redirects the fate of RPCs. Previously, the researchers showed that Neurod1 can replace the function of Atoh7 in specifying retinal ganglion cells (RGCs), which suggests that Atoh7-expressing RPCs are pre-programmed to produce RGCs. Now, they report that insertion of Atoh7 into the Neurod1 locus reprogrammes Neurod1-expressing RPCs, which normally produce amacrine and photoreceptor cells, into RGCs. Thus, Atoh7 acts dominantly to specify an RGC fate. The researchers also identify an Atoh7-dependent enhancer within its target gene Nrxn3 that is used by Atoh7 but not by Neurod1 in the developing retina. Together, these results provide new insights into the specification of retinal cells by proneural bHLH factors.
