EGFR signaling is required for regenerative proliferation in the cochlea: conservation in birds and mammals.
EGFR signaling is required for regenerative proliferation in the cochlea: conservation in birds and mammals.
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DOI：
10.1016/j.ydbio.2011.12.035
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发表时间：
2012-03-01
影响因子：
2.7
通讯作者：
Segil N
中科院分区：
文献类型：
--
作者：
White PM;Stone JS;Groves AK;Segil N
在鸟类受损的听觉器官中，支持细胞的增殖和转分化导致感觉毛细胞的稳健再生。相比之下，哺乳动物失去的听觉毛细胞不会再生，导致永久性听力损失。尽管哺乳动物的再生失败，我们以前已经表明，围产期小鼠支持细胞具有潜在的细胞分裂潜力。在这里，我们表明，在一个子集的支持细胞标记的p75，EGFR信号是必需的增殖，这种要求是保守的鸟类和哺乳动物之间。纯化的p75+小鼠支持细胞表达EGF信号通路的受体和配体，并且它们在培养物中的增殖可以用EGFR抑制剂AG1478阻断。类似地，在培养的鸡基底乳头中，支持响应于毛细胞消融的细胞增殖需要EGFR信号传导。此外，我们表明，EGFR信号在p75+小鼠支持细胞的下调细胞周期抑制剂p27 Kip1（CDKN1b），使细胞周期重新进入所需的。总之，我们的数据表明，涉及EGFR信号转导的保守机制控制鸟类和哺乳动物的听觉支持细胞的增殖，并可能代表未来毛细胞再生策略的目标。
Proliferation and transdifferentiaton of supporting cells in the damaged auditory organ of birds leads to robust regeneration of sensory hair cells. In contrast, regeneration of lost auditory hair cells does not occur in deafened mammals, resulting in permanent hearing loss. In spite of this failure of regeneration in mammals, we have previously shown that the perinatal mouse supporting cells harbor a latent potential for cell division. Here we show that in a subset of supporting cells marked by p75, EGFR signaling is required for proliferation, and this requirement is conserved between birds and mammals. Purified p75+ mouse supporting cells express receptors and ligands for the EGF signaling pathway, and their proliferation in culture can be blocked with the EGFR inhibitor AG1478. Similarly, in cultured chicken basilar papillae, supporting cell proliferation in response to hair cell ablation requires EGFR signaling. In addition, we show that EGFR signaling in p75+ mouse supporting cells is required for the down-regulation of the cell cycle inhibitor p27Kip1 (CDKN1b) to enable cell cycle re-entry. Taken together, our data suggest that a conserved mechanism involving EGFR signaling governs proliferation of auditory supporting cells in birds and mammals and may represent a target for future hair cell regeneration strategies.
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影响因子：
2.9
作者：
Brignull HR;Raible DW;Stone JS
通讯作者：
Stone JS
影响因子：
--
作者：
Li, HW;Corrales, CE;Wang, ZM;Zhao, YL;Wang, YC;Liu, H;Heller, S
通讯作者：
Heller, S
DOI：
10.1523/jneurosci.5154-09.2010
发表时间：
2010-01-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
McCullar JS;Ty S;Campbell S;Oesterle EC
通讯作者：
Oesterle EC
DOI：
10.1523/jneurosci.5456-10.2011
发表时间：
2011-03-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Alvarado DM;Hawkins RD;Bashiardes S;Veile RA;Ku YC;Powder KE;Spriggs MK;Speck JD;Warchol ME;Lovett M
通讯作者：
Lovett M
影响因子：
6.5
作者：
CLAUSEN, OPF;KIRKHUS, B;SCHJOLBERG, AR
通讯作者：
SCHJOLBERG, AR