Mash1 and Ngn1 control distinct steps of determination and differentiation in the olfactory sensory neuron lineage.

bHLH transcription factors are expressed sequentially during the development of neural lineages, suggesting that they operate in genetic cascades. In the olfactory epithelium, the proneural genes Mash1 and neurogenin1 are expressed at distinct steps in the same olfactory sensory neuron lineage. Here, we show by loss-of-function analysis that both genes are required for the generation of olfactory sensory neurons. However, their mutant phenotypes are strikingly different, indicating that they have divergent functions. In Mash1 null mutant mice, olfactory progenitors are not produced and the Notch signalling pathway is not activated, establishing Mash1 as a determination gene for olfactory sensory neurons. In neurogenin1 null mutant mice, olfactory progenitors are generated but they express only a subset of their normal repertoire of regulatory molecules and their differentiation is blocked. Thus neurogenin1 is required for the activation of one of several parallel genetic programs functioning downstream of Mash1 in the differentiation of olfactory sensory neurons. These results illustrate the versatility of neural bHLH genes which adopt either a determination or a differentiation function, depending primarily on the timing of their expression in neural progenitors.