Eya1-Six1 interaction is sufficient to induce hair cell fate in the cochlea by activating Atoh1 expression in cooperation with Sox2.
Eya1-Six1 interaction is sufficient to induce hair cell fate in the cochlea by activating Atoh1 expression in cooperation with Sox2.
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DOI：
10.1016/j.devcel.2011.12.006
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发表时间：
2012-02-14
影响因子：
11.8
通讯作者：
Xu, Pin-Xian
中科院分区：
文献类型：
--
作者：
Ahmed, Mohi;Wong, Elaine Y. M.;Sun, Jianbo;Xu, Jinshu;Wang, Feng;Xu, Pin-Xian
内耳毛细胞分化需要Atoh 1功能，而Eya 1，Six 1和Sox 2在感觉祖细胞中共表达，这些基因的突变导致感觉神经性听力损失。然而，这些基因是如何在功能上联系起来的，以及控制毛细胞诱导的转录网络仍然不清楚。在这里，我们表明，Eya 1/Six 1是必要的毛细胞发育和它们的共表达在小鼠耳蜗外植体是足以诱导毛细胞的命运在非感觉上皮细胞表达低水平的Sox 2激活不仅Atoh 1依赖，但也不依赖的途径，这两种途径诱导Pou 4f 3，以促进毛细胞分化。Sox 2与Eya 1/Six 1合作，通过直接结合Atoh 1增强子中保守的Sox和Six结合位点协同激活Atoh 1转录，这些蛋白质物理相互作用。我们的研究结果表明，Sox 2，Six 1和Eya 1蛋白之间的直接和合作的相互作用协调Atoh 1的表达，以指定毛细胞的命运。
Inner ear hair cell differentiation requires Atoh1 function, while Eya1, Six1 and Sox2 are coexpressed in sensory progenitors and mutations in these genes cause sensorineural hearing loss. However, how these genes are linked functionally and the transcriptional networks controlling hair cell induction remain unclear. Here, we show that Eya1/Six1 are necessary for hair cell development and their coexpression in mouse cochlear explants is sufficient to induce hair cell fate in the nonsensory epithelium expressing low level Sox2 by activating not only Atoh1-dependent but also -independent pathways and that both pathways induce Pou4f3 to promote hair cell differentiation. Sox2 cooperates with Eya1/Six1 to synergistically activate Atoh1 transcription via direct binding to the conserved Sox- and Six-binding sites in Atoh1 enhancers and these proteins physically interact. Our findings demonstrate that direct and cooperative interactions between the Sox2, Six1 and Eya1 proteins coordinate Atoh1 expression to specify hair cell fate.
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DOI：
10.1073/pnas.0808175105
发表时间：
2008-11-25
影响因子：
11.1
作者：
Dabdoub, Alain;Puligilla, Chandrakala;Kelley, Matthew W.
通讯作者：
Kelley, Matthew W.
影响因子：
9.8
作者：
Hoskins, Bethan E.;Cramer, Carl H., II;Hildebrandt, Friedhelm
通讯作者：
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DOI：
10.1073/pnas.95.24.14220
发表时间：
1998-11-24
影响因子：
11.1
作者：
Spitz, F;Demignon, J;Maire, P
通讯作者：
Maire, P
影响因子：
16.2
作者：
Machold, R;Fishell, G
通讯作者：
Fishell, G
影响因子：
3.5
作者：
Hertzano, R;Montcouquiol, M;Avraham, KB
通讯作者：
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