Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear
Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear
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DOI：
10.1242/dev.02284
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发表时间：
2006-04-01
期刊：
影响因子：
4.6
通讯作者：
Lewis, J
中科院分区：
文献类型：
--
作者：
Brooker, R;Hozumi, K;Lewis, J
内耳上皮中的每一个感觉片都是毛细胞和支持细胞的镶嵌体。Notch信号被认为通过侧抑制来控制这种分化模式。然而，最近在小鸡身上的实验表明，Notch信号也有一个先前的功能--诱导性而不是诱导性。形成分化细胞产生的前感觉片。几个Notch配体在每个斑块中表达，但它们与Notch信号传导的两种功能相关的单独作用尚不清楚。我们使用Cre-LoxP方法敲除小鼠耳中的两种配体Delta 1（DII 1）和Jagged 1（Jag 1）。在DII 1的情况下，听觉毛细胞发育早期和过量，与侧抑制假说一致。在Jag 1的情况下，相比之下，这些细胞的总数大大减少，耳蜗外毛细胞和前庭毛细胞的一些群体的完全损失，表明Jag 1是所需的前感觉诱导功能的Notch。然而，耳蜗内毛细胞的数量几乎增加了一倍。这与细胞周期抑制剂p27 Kip 1（Cdkn 1b）表达的丧失相关，表明Jag 1的信号传导也需要限制前感觉细胞的增殖，并且该群体的核心部分的前感觉特征独立于Jag 1-Notch信号传导而建立。我们的研究结果证实，Notch信号在耳朵有不同的前感觉和侧抑制功能，不同的配体主要负责。
Each of the sensory patches in the epithelium of the inner ear is a mosaic of hair cells and supporting cells. Notch signalling is thought to govern this pattern of differentiation through lateral inhibition. Recent experiments in the chick suggest, however, that Notch signalling also has a prior function-inductive rather than inhibitory-in de. ning the prosensory patches from which the differentiated cells arise. Several Notch ligands are expressed in each patch, but their individual roles in relation to the two functions of Notch signalling are unclear. We have used a Cre-LoxP approach to knock out two of these ligands, Delta1 (DII1) and Jagged1 (Jag1), in the mouse ear. In the absence of DII1, auditory hair cells develop early and in excess, in agreement with the lateral inhibition hypothesis. In the absence of Jag1, by contrast, the total number of these cells is strongly reduced, with complete loss of cochlear outer hair cells and some groups of vestibular hair cells, indicating that Jag1 is required for the prosensory inductive function of Notch. The number of cochlear inner hair cells, however, is almost doubled. This correlates with loss of expression of the cell cycle inhibitor p27Kip1 (Cdkn1b), suggesting that signalling by Jag1 is also needed to limit proliferation of prosensory cells, and that there is a core part of this population whose prosensory character is established independently of Jag1-Notch signalling. Our findings confirm that Notch signalling in the ear has distinct prosensory and lateral-inhibitory functions, for which different ligands are primarily responsible.