Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells
Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells
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DOI：
10.1073/pnas.1222341110
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发表时间：
2013-08-20
影响因子：
11.1
通讯作者：
Wu, Doris K.
中科院分区：
文献类型：
--
作者：
Bok, Jinwoong;Zenczak, Colleen;Wu, Doris K.
中枢神经系统的神经前体细胞经历连续的末梢分裂的时间波，每一次分裂之后不久就开始细胞分化。哺乳动物耳蜗中的Corti器官发育不同，例如顶端的前体是第一个退出细胞周期的，但最后一个开始分化为机械感觉毛细胞。在小鼠中使用组织特异性敲除方法，我们发现这种独特的感觉细胞发育的时间模式需要邻近的听觉（螺旋）神经节作为信号分子Sonic hedgehog （Shh）的来源。在缺乏这种信号的情况下，耳蜗导管缩短，感觉毛细胞前体提前退出细胞周期，毛细胞分化密切跟随细胞周期退出，其方向与细胞周期退出相似。发育中的螺旋神经节中Shh表达的限制与其靠近生长中的耳蜗管区域之间的动态关系决定了毛细胞前体有丝分裂的最终时间及其随后的分化。
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.