miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells
miR-96 regulates the progression of differentiation in mammalian cochlear inner and outer hair cells
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DOI：
10.1073/pnas.1016646108
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发表时间：
2011-02-08
影响因子：
11.1
通讯作者：
Marcotti, Walter
中科院分区：
文献类型：
--
作者：
Kuhn, Stephanie;Johnson, Stuart L.;Marcotti, Walter
MicroRNAs(MiRNAs)是一种小的非编码RNA，能够调控许多生物过程中涉及的广泛的蛋白质编码基因。MIR-96是一种感觉器官特异性的miRNA，在哺乳动物耳蜗组织发育过程中表达。MiR-96基因突变会导致人类和小鼠的非综合征性进行性听力损失。小鼠突变体Dinuendo在Mir96基因的种子区域有一个单一的碱基变化，导致许多基因的表达发生广泛的变化。我们利用这个突变体来探索miR-96在听觉器官成熟中的作用。我们发现，突变的感觉毛细胞的生理发育在出生后大约一天就停止了，在它们的生物物理分化为内毛细胞和外毛细胞之前。此外，在miR-96突变体中，未能发生毛细胞立体纤毛束的成熟和耳蜗内听神经连接的重塑。我们得出结论，miR-96调节耳蜗毛细胞的生理和形态分化的进程，并因此协调哺乳动物听觉系统最独特的功能细化之一。
MicroRNAs (miRNAs) are small noncoding RNAs able to regulate a broad range of protein-coding genes involved in many biological processes. miR-96 is a sensory organ-specific miRNA expressed in the mammalian cochlea during development. Mutations in miR-96 cause nonsyndromic progressive hearing loss in humans and mice. The mouse mutant diminuendo has a single base change in the seed region of the Mir96 gene leading to widespread changes in the expression of many genes. We have used this mutant to explore the role of miR-96 in the maturation of the auditory organ. We found that the physiological development of mutant sensory hair cells is arrested at around the day of birth, before their biophysical differentiation into inner and outer hair cells. Moreover, maturation of the hair cell stereocilia bundle and remodelling of auditory nerve connections within the cochlea fail to occur in miR-96 mutants. We conclude that miR-96 regulates the progression of the physiological and morphological differentiation of cochlear hair cells and, as such, coordinates one of the most distinctive functional refinements of the mammalian auditory system.