Notch signaling in the development of the inner ear:: Lessons from Drosophila

Notch signaling in the development of the inner ear:: Lessons from Drosophila
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DOI:
10.1073/pnas.97.22.11692
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发表时间:
2000-10-24
影响因子:
11.1
通讯作者:
Lewis, J
Lewis, J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Eddison, M;Le Roux, I;Lewis, J

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脊椎动物耳朵里的感觉片可以和苍蝇的机械感觉刚毛相比较。这种比较导致发现,由Notch细胞-细胞信号通路介导的侧向抑制,首先在果蝇中表征,对刚毛发育至关重要,也在控制感觉毛细胞和支持细胞的模式中起关键作用。我们审查的论点,考虑的感觉补丁的脊椎动物的耳朵和刚毛的昆虫是同源结构,从一个共同的祖先mechanosensory器官进化而来,我们更密切地研究Notch信号在每个系统中的作用。使用病毒载体在鸡耳中错误表达Notch途径的成分,我们表明,一个简单的横向抑制模型的基础上反馈调节的Notch配体三角洲是不够的,耳朵就像它是为飞鬃。Notch配体Serrate 1在耳中的支持细胞中表达,受侧向诱导而不是侧向抑制的调节;成为毛细胞的承诺并不简单地由新生毛细胞的邻居中Notch配体Delta 1,Serrate 1和Serrate 2的表达水平控制;并且至少一种能够阻断侧向抑制的接受的因子Numb集中在毛细胞中。这些发现加强了脊椎动物耳朵和苍蝇刚毛之间的相似之处,并显示了昆虫系统的研究如何帮助我们了解脊椎动物。
The sensory patches in the ear of a vertebrate can be compared with the mechanosensory bristles of a fly. This comparison has led to the discovery that lateral inhibition mediated by the Notch cell-cell signaling pathway, first characterized in Drosophila and crucial for bristle development, also has a key role in controlling the pattern of sensory hair cells and supporting cells in the ear. We review the arguments for considering the sensory patches of the vertebrate ear and bristles of the insect to be homologous structures, evolved from a common ancestral mechanosensory organ, and we examine more closely the role of Notch signaling in each system. Using viral vectors to misexpress components of the Notch pathway in the chick ear, we show that a simple lateral-inhibition model based on feedback regulation of the Notch ligand Delta is inadequate,for the ear just as it is for the fly bristle. The Notch ligand Serrate1, expressed in supporting cells in the ear, is regulated by lateral induction, not lateral inhibition; commitment to become a hair cell is not simply controlled by levels of expression of the Notch ligands Delta1, Serrate1, and Serrate2 in the neighbors of the nascent hair cell; and at least one factor, Numb, capable of blocking reception of lateral inhibition is concentrated in hair cells. These findings reinforce the parallels between the vertebrate ear and the fly bristle and show how study of the insect system can help us understand the vertebrate.