Hair cell fate decisions in cochlear development and regeneration.

Hair cell fate decisions in cochlear development and regeneration.
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DOI:
10.1016/j.heares.2010.04.012
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发表时间:
2010-07
期刊:
影响因子:
2.8
通讯作者:
Kaiser, Christina L.
Kaiser, Christina L.
中科院分区:
医学1区
文献类型:
--
作者:
Cotanche, Douglas A.;Kaiser, Christina L.

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20世纪80年代后期,鸟类耳蜗毛细胞再生的发现以及分子和发育生物学新技术的同步发展,使人们对理解鸟类和哺乳动物胚胎耳蜗毛细胞发育和成熟鸟类耳蜗再生的遗传机制产生了新的兴趣。许多实验室的研究表明,内耳的发育利用一系列复杂的遗传信号和途径来产生内耳器官,指定细胞身份,并建立内耳中发现的神经支配模式。最近的研究表明,Notch信号通路、Atoh1/Hes信号级联、干细胞标记物Sox2和一些非常规的肌球蛋白运动蛋白被用于调节内耳发育的不同步骤。虽然已经从突变和敲除小鼠耳蜗的研究中确定了许多参与这些途径的单个基因,但需要探索所有这些信号在指导这一过程的单一系统程序中的相互作用。我们不仅需要知道哪些基因参与其中,还需要了解它们的基因产物如何在结构和时间框架中相互作用,以指导毛细胞并支持细胞分化和成熟。
The discovery of avian cochlear hair cell regeneration in the late 1980’s and the concurrent development of new techniques in molecular and developmental biology generated a renewed interest in understanding the genetic mechanisms that regulate hair cell development in the embryonic avian and mammalian cochlea and regeneration in the mature avian cochlea. Research from many labs has demonstrated that the development of the inner ear utilizes a complex series of genetic signals and pathways to generate the endorgans, specify cell identities, and establish innervation patterns found in the inner ear. Recent studies have shown that the Notch signaling pathway, the Atoh1/Hes signaling cascade, the stem cell marker Sox2, and some of the unconventional myosin motor proteins are utilized to regulate distinct steps in inner ear development. While many of the individual genes involved in these pathways have been identified from studies of mutant and knockout mouse cochleae, the interplay of all these signals into a single systemic program that directs this process needs to be explored. We need to know not only what genes are involved, but understand how their gene products interact with one another in a structural and temporal framework to guide hair cell and supporting cell differentiation and maturation.
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