Cau Elise, Casarosa Simona, Guillemot François
IGBMC, 1 rue Laurent Fries, 67404 Illkirch cedex, CU de Strasbourg, France.
Development. 2002 Apr;129(8):1871-80. doi: 10.1242/dev.129.8.1871.
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.
bHLH转录因子在神经谱系发育过程中依次表达，这表明它们在基因级联反应中发挥作用。在嗅觉上皮中，神经源性基因Mash1和神经生成素1在同一嗅觉感觉神经元谱系的不同阶段表达。在这里，我们通过功能丧失分析表明，这两个基因都是生成嗅觉感觉神经元所必需的。然而，它们的突变表型却显著不同，这表明它们具有不同的功能。在Mash1基因敲除突变小鼠中，嗅觉祖细胞未产生，Notch信号通路未被激活，这确立了Mash1作为嗅觉感觉神经元的决定基因。在神经生成素1基因敲除突变小鼠中，嗅觉祖细胞产生了，但它们只表达其正常调控分子库中的一部分，并且它们的分化被阻断。因此，神经生成素1是在嗅觉感觉神经元分化过程中，激活Mash1下游几个平行遗传程序之一所必需的。这些结果说明了神经bHLH基因的多功能性，它们主要根据在神经祖细胞中的表达时间，采用决定或分化功能。
