The developmental genetics of auditory hair cells.
The developmental genetics of auditory hair cells.
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听觉毛细胞的发育遗传学。
DOI：
10.1093/hmg/ddh249
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
Lovett,Michael
中科院分区：
文献类型：
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作者：
Hawkins,RDavid;Lovett,Michael
听力毛细胞（AHCs）的损失是人类耳聋的主要原因。为了通过基因或干细胞治疗来纠正听力损失，人们已经付出了相当大的努力来揭示这些声音的机械换能器是如何被指定的。最近对信号级联的研究，特别是横向抑制和平面细胞极性，已经开始将一些已知的通路联系在一起。小鼠和人类中引起听力和/或平衡障碍的突变也揭示了ahc是如何被指定、维持和处理离子通量的。对其中一些基因的研究，正开始为更复杂的晚发性听力损失形式的遗传学提供见解。在解决听觉生物学的一些长期目标方面也取得了进展。Cadherin23已被鉴定为AHC立体纤毛尖端连接的一个组成部分，并且在鉴定难以捉摸的AHC机械受体通道方面取得了进展。在内耳基因治疗和胚胎干细胞工程方面也取得了初步进展，以实现最终的细胞治疗。哺乳动物不能再生ahc，但鸟类和其他低等脊椎动物可以。基因组工具现在被用于解决这个问题，目的是破译这种再生能力的分子基础。新的基因组工具和许多小鼠和鸡的胚胎学和遗传资源的结合，将越来越多地为AHCs的编程和维持提供新的见解。
Loss of auditory hair cells (AHCs) is a major cause of human deafness. Considerable effort has been devoted to unraveling how these mechanotransducers of sound are specified, with a view to correcting hearing loss by gene or stem cell therapies. Recent work on signaling cascades, particularly lateral inhibition and planar cell polarity, has begun to tie together some of the known pathways. Mutations in mice and humans that cause hearing and/or balance disorders are also shedding light on how AHCs are specified and, maintained and handle ion flux. Studies on some of these genes are beginning to provide insights into the more complex genetics of later onset forms of hearing loss. Progress has also been made in solving some long-term goals of auditory biology. Cadherin23 has been identified as a component of AHC stereocilia tip links, and progress has been made towards identifying the elusive AHC mechanoreceptor channel. Preliminary steps have also been taken towards inner-ear gene therapy, and in the engineering of embryonic stem cells for eventual cell therapies. Mammals cannot regenerate AHCs, but birds and other lower vertebrates can. Genomic tools have now been brought to bear on this problem with the aim of deciphering the molecular basis of this regenerative capability. The combination of new genomic tools and the many mouse and chicken embryological and genetic resources should increasingly provide new insights into how AHCs are programed and maintained.