Math1 regulates development of the sensory epithelium in the mammalian cochlea
Math1 regulates development of the sensory epithelium in the mammalian cochlea
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DOI：
10.1038/nn1349
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发表时间：
2004-12-01
影响因子：
25
通讯作者：
Kelley, MW
中科院分区：
文献类型：
--
作者：
Woods, C;Montcouquiol, M;Kelley, MW
转录因子Math1（由基因Atoh1编码，也称为Math1）是内耳机械感觉毛细胞形成所必需的；然而，其具体的分子作用尚不清楚。本研究表明，小鼠中缺乏Math1会导致耳蜗感觉上皮的形成完全中断，包括毛细胞和相关支持细胞的发育。此外，Math1在耳蜗非感觉区域的异位表达足以诱导包含毛细胞和支持细胞的感觉簇的形成。这些细胞簇的形成依赖于抑制性相互作用，最有可能是通过Notch通路，以及诱导相互作用，诱导细胞通过独立于Math1的通路发育为支持细胞。这些结果表明，Math1在发育中的耳蜗中启动诱导和抑制信号，调节感觉上皮的整体形成。
The transcription factor Math1 (encoded by the gene Atoh1, also called Math1) is required for the formation of mechanosensory hair cells in the inner ear; however, its specific molecular role is unknown. Here we show that absence of Math1 in mice results in a complete disruption of formation of the sensory epithelium of the cochlea, including the development of both hair cells and associated supporting cells. In addition, ectopic expression of Math1 in nonsensory regions of the cochlea is sufficient to induce the formation of sensory clusters that contain both hair cells and supporting cells. The formation of these clusters is dependent on inhibitory interactions mediated, most probably, through the Notch pathway, and on inductive interactions that recruit cells to develop as supporting cells through a pathway independent of Math1. These results show that Math1 functions in the developing cochlea to initiate both inductive and inhibitory signals that regulate the overall formation of the sensory epithelia.