Inhibitors of differentiation and DNA binding (Ids) regulate Math1 and hair cell formation during the development of the organ of Corti
Inhibitors of differentiation and DNA binding (Ids) regulate Math1 and hair cell formation during the development of the organ of Corti
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DOI：
10.1523/jneurosci.3859-05.2006
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发表时间：
2006-01-11
影响因子：
5.3
通讯作者：
Kelley, MW
中科院分区：
文献类型：
--
作者：
Jones, JM;Montcouquiol, M;Kelley, MW
碱性螺旋-环-螺旋（bHLH）转录因子Math 1（也称为Atoh 1）对于哺乳动物耳蜗中的毛细胞发育是必需的和足够的（Berlovet al.，1999; Zheng和Gao，2000）。以前的研究表明，Math 1表达的动态模式在调节机械感觉毛细胞的数量和位置中起着关键作用。然而，调节耳蜗内Math 1的时间和空间表达的因素尚不清楚。已知bHLH相关的分化抑制剂和DNA结合（Id）蛋白在许多不同的系统中负调节许多bHLH转录因子，包括Math 1。因此，Id蛋白是调节耳蜗中Math 1的良好候选者。PCR和原位杂交的结果表明，Id 1，Id 2和Id 3的耳蜗导管内表达的模式是一致的，在毛细胞发育的调节作用。特别是，表达的Ids和Math 1重叠在耳蜗前体细胞细胞分化，但一个特定的下调Id的表达在个别细胞分化为毛细胞。此外，在毛细胞分化期间维持Ids表达的祖细胞被抑制发育为毛细胞。这些结果表明Ids在发育中的耳蜗中调节Math 1的表达和毛细胞分化中起关键作用。
The basic helix-loop-helix (bHLH) transcription factor Math1 (also called Atoh1) is both necessary and sufficient for hair cell development in the mammalian cochlea (Bermingham et al., 1999; Zheng and Gao, 2000). Previous studies have demonstrated that a dynamic pattern of Math1 expression plays a key role in regulating the number and position of mechanosensory hair cells. However, the factors that regulate the temporal and spatial expression of Math1 within the cochlea are unknown. The bHLH-related inhibitors of differentiation and DNA binding (Id) proteins are known to negatively regulate many bHLH transcription factors, including Math1, in a number of different systems. Therefore, Id proteins are good candidates for regulating Math1 in the cochlea. Results from PCR and in situ hybridization indicate that Id1, Id2, and Id3 are expressed within the cochlear duct in a pattern that is consistent with a role in regulation of hair cell development. In particular, expression of Ids and Math1 overlapped in cochlear progenitor cells before cellular differentiation, but a specific downregulation of Id expression was observed in individual cells that differentiated as hair cells. In addition, progenitor cells in which the expression of Ids was maintained during the time period for hair cell differentiation were inhibited from developing as hair cells. These results indicate a key role for Ids in the regulation of expression of Math1 and hair cell differentiation in the developing cochlea.