Multiple roles of notch signaling in the regulation of epidermal development
Multiple roles of notch signaling in the regulation of epidermal development
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DOI：
10.1016/j.devcel.2008.01.017
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发表时间：
2008-04-01
影响因子：
11.8
通讯作者：
Osawa, Masatake
中科院分区：
文献类型：
--
作者：
Moriyama, Mariko;Durham, Andre-Dante;Osawa, Masatake
最近的研究表明，Notch信号在表皮发育中起着重要的作用，但其潜在的分子机制尚不清楚。在这里，通过整合Notch受体和Hes1的功能丧失和功能获得的研究，我们描述了关于Notch信号在表皮发育中作用的分子信息。我们发现，Notch信号通过独立于Hes1的机制决定棘细胞的命运并诱导末端分化，但Hes1是维持棘细胞未成熟状态所必需的。Noch信号通过诱导Ascl2的表达促进末端分化，同时通过Hes1抑制Ascl2的表达以抑制末端的提前分化。尽管Hes1在表皮发育中起着关键作用，但移植到成年小鼠体内的Hes1缺失表皮并未显示出明显的缺陷，提示Hes1的这种作用可能仅限于发育阶段。总体而言，我们得出结论，在表皮发育过程中，Notch信号协调着超基底细胞中分化和未成熟程序之间的平衡。
Recent studies have shown that Notch signaling plays an important role in epidermal development, but the underlying molecular mechanisms remain unclear. Here, by integrating loss- and gain -of-function studies of Notch receptors and Hes1, we describe molecular information about the role of Notch signaling in epidermal development. We show that Notch signaling determines spinous cell fate and induces terminal differentiation by a mechanism independent of Hes1, but Hes1 is required for maintenance of the immature state of spinous cells. Notch signaling induces Ascl2 expression to promote terminal differentiation, while simultaneously repressing Ascl2 through Hes1 to inhibit premature terminal differentiation. Despite the critical role of Hes1 in epidermal development, Hes1 null epidermis transplanted to adult mice showed no obvious defects, suggesting that this role of Hes1 may be restricted to developmental stages. Overall, we conclude that Notch signaling orchestrates the balance between differentiation and immature programs in suprabasal cells during epidermal development.