Department of Anatomy, Department of Otorhinolaryngology, BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):13869-74. doi: 10.1073/pnas.1222341110. Epub 2013 Aug 5.
Neural precursor cells of the central nervous system undergo successive temporal waves of terminal division, each of which is soon followed by the onset of cell differentiation. The organ of Corti in the mammalian cochlea develops differently, such that precursors at the apex are the first to exit from the cell cycle but the last to begin differentiating as mechanosensory hair cells. Using a tissue-specific knockout approach in mice, we show that this unique temporal pattern of sensory cell development requires that the adjacent auditory (spiral) ganglion serve as a source of the signaling molecule Sonic hedgehog (Shh). In the absence of this signaling, the cochlear duct is shortened, sensory hair cell precursors exit from the cell cycle prematurely, and hair cell differentiation closely follows cell cycle exit in a similar apical-to-basal direction. The dynamic relationship between the restriction of Shh expression in the developing spiral ganglion and its proximity to regions of the growing cochlear duct dictates the timing of terminal mitosis of hair cell precursors and their subsequent differentiation.
中枢神经系统的神经前体细胞经历连续的终末分裂时相，每个时相之后很快就会出现细胞分化。哺乳动物耳蜗中的 Corti 器官发育方式不同，因此，顶端的前体细胞是最早退出细胞周期但最后开始分化为机械敏感毛细胞的细胞。我们通过在小鼠中使用组织特异性敲除方法表明，这种独特的感觉细胞发育的时间模式要求相邻的听觉（螺旋）神经节作为信号分子 Sonic hedgehog (Shh) 的来源。在没有这种信号的情况下，耳蜗管缩短，感觉毛细胞前体细胞过早退出细胞周期，并且毛细胞分化紧随细胞周期退出，呈现出从顶端到底部的相似方向。发育中的螺旋神经节中 Shh 表达的限制及其与生长中的耳蜗管区域的接近程度之间的动态关系决定了毛细胞前体细胞的终末有丝分裂及其随后分化的时间。
