Cai Tiantian, Groves Andrew K
Program in Developmental Biology, Baylor College of Medicine, Houston, USA.
Department of Neuroscience, Baylor College of Medicine, Houston, USA.
Mol Neurobiol. 2015 Dec;52(3):1315-1329. doi: 10.1007/s12035-014-8925-0. Epub 2014 Oct 23.
Atonal genes are basic helix-loop-helix transcription factors that were first identified as regulating the formation of mechanoreceptors and photoreceptors in Drosophila. Isolation of vertebrate homologs of atonal genes has shown these transcription factors to play diverse roles in the development of neurons and their progenitors, gut epithelial cells, and mechanosensory cells in the inner ear and skin. In this article, we review the molecular function and regulation of atonal genes and their targets, with particular emphasis on the function of Atoh1 in the development, survival, and function of hair cells of the inner ear. We discuss cell-extrinsic signals that induce Atoh1 expression and the transcriptional networks that regulate its expression during development. Finally, we discuss recent work showing how identification of Atoh1 target genes in the cerebellum, spinal cord, and gut can be used to propose candidate Atoh1 targets in tissues such as the inner ear where cell numbers and biochemical material are limiting.
无调性基因是碱性螺旋-环-螺旋转录因子,最初被鉴定为调控果蝇机械感受器和光感受器的形成。无调性基因的脊椎动物同源物的分离表明,这些转录因子在神经元及其祖细胞、肠道上皮细胞以及内耳和皮肤中的机械感觉细胞的发育中发挥着多种作用。在本文中,我们综述了无调性基因及其靶标的分子功能和调控,特别强调了Atoh1在内耳毛细胞发育、存活和功能中的作用。我们讨论了诱导Atoh1表达的细胞外信号以及在发育过程中调控其表达的转录网络。最后,我们讨论了最近的研究工作,这些研究表明如何利用在小脑、脊髓和肠道中鉴定出的Atoh1靶基因,来推测在内耳等细胞数量和生化物质有限的组织中的候选Atoh1靶标。