Notch signalling pathway mediates hair cell development in mammalian cochlea
Notch signalling pathway mediates hair cell development in mammalian cochlea
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DOI：
10.1038/6804
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发表时间：
1999-03-01
期刊：
影响因子：
30.8
通讯作者：
Kelley, MW
中科院分区：
文献类型：
--
作者：
Lanford, PJ;Lan, Y;Kelley, MW
哺乳动物的耳蜗包含一个不变的感觉毛细胞和非感觉支持细胞的马赛克，让人想起无脊椎动物的结构，如果蝇的复眼（1，2）。哺乳动物耳蜗（Corti器官）的感觉上皮包含四排机械感觉毛细胞：一排内毛细胞和三排外毛细胞。每一个毛细胞都被一个中间的支持细胞与下一个分开，形成一个不变的和交替的马赛克，延伸到耳蜗管的长度（1）。先前的结果表明，耳蜗嵌合体中细胞命运的确定是通过相邻祖细胞之间的抑制性相互作用发生的（3-5）（侧抑制）。耳蜗上皮细胞似乎构成了一个发育等效组，其中发育中的毛细胞通过侧抑制抑制其近邻细胞的分化（6）。这些相互作用可能是通过Notch信号通路介导的，Notch信号通路是一种参与决定各种细胞命运的分子机制（7-9）。在这里，我们表明编码受体蛋白Notch 1及其配体laged 2的基因在发育中的感觉上皮中的交替细胞类型中表达。此外，Jag 2的基因缺失导致感觉毛细胞的显著增加，可能是由于Notch激活减少的结果。这些结果为Notch介导的侧抑制在哺乳动物系统中提供了直接证据，并支持Notch在耳蜗嵌合体发育中的作用。
The mammalian cochlea contains an invariant mosaic of sensory hair cells and non-sensory supporting cells reminiscent of invertebrate structures such as the compound eye in Drosophila melanogaster(1,2). The sensory epithelium in the mammalian cochlea (the organ of Corti) contains four rows of mechanosensory hair cells: a single row of inner hair cells and three rows of outer hair cells. Each hair cell is separated from the next by an interceding supporting cell, forming an invariant and alternating mosaic that extends the length of the cochlear duct(1). Previous results suggest that determination of cell fates in the cochlear mosaic occurs via inhibitory interactions between adjacent progenitor cells(3-5) (lateral inhibition). Cells populating the cochlear epithelium appear to constitute a developmental equivalence group in which developing hair cells suppress differentiation in their immediate neighbours through lateral inhibition(6). These interactions may be mediated through the Notch signalling pathway, a molecular mechanism that is involved in the determination of a variety of cell fates(7-9) Here we show that genes encoding the receptor protein Notch1 and its ligand, lagged 2, are expressed in alternating cell types in the developing sensory epithelium. In addition, genetic deletion of Jag2 results in a significant increase in sensory hair cells, presumably as a result of a decrease in Notch activation. These results provide direct evidence for Notch-mediated lateral inhibition in a mammalian system and support a role for Notch in the development of the cochlear mosaic.