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非洲爪蟾中果蝇无翅抑制因子的同源物在初级神经发生过程中介导Notch信号通路。

The Xenopus homolog of Drosophila Suppressor of Hairless mediates Notch signaling during primary neurogenesis.

作者信息

Wettstein D A, Turner D L, Kintner C

机构信息

Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037-1099, USA.

出版信息

Development. 1997 Feb;124(3):693-702. doi: 10.1242/dev.124.3.693.

Abstract

The X-Notch-1 receptor, and its putative ligand, X-Delta-1, are thought to mediate an inhibitory cell-cell interaction, called lateral inhibition, that limits the number of primary neurons that form in Xenopus embryos. The expression of Xenopus ESR-1, a gene related to Drosophila Enhancer of split, appears to be induced by Notch signaling during this process. To determine how the activation of X-Notch-1 induces ESR-1 expression and regulates primary neurogenesis, we isolated the Xenopus homolog of Suppressor of Hairless (X-Su(H)), a component of the Notch signaling pathway in Drosophila. Using animal cap assays, we show that X-Su(H) induces ESR-1 expression, perhaps directly, when modified by the addition of ankyrin repeats. Using a DNA binding mutant of X-Su(H), we show that X-Su(H) activity is required for induction of ESR-1. Finally, expression of the DNA binding mutant in embryos leads to a neurogenic phenotype as well as increased expression of both X-Delta-1 and XNGNR1, a proneural gene expressed during primary neurogenesis. These results suggest that activation of X-Su(H) is a key step in the Notch signaling pathway during primary neurogenesis in Xenopus embryos.

摘要

X-Notch-1受体及其假定的配体X-Delta-1被认为介导一种抑制性细胞间相互作用,称为侧向抑制,这种抑制作用限制了非洲爪蟾胚胎中形成的初级神经元数量。非洲爪蟾ESR-1基因与果蝇的分裂增强子相关,在这一过程中其表达似乎由Notch信号诱导。为了确定X-Notch-1的激活如何诱导ESR-1表达并调节初级神经发生,我们分离出了果蝇Notch信号通路的一个组分——无毛抑制因子(X-Su(H))的非洲爪蟾同源物。通过动物帽实验,我们发现当添加锚蛋白重复序列进行修饰时,X-Su(H)可能直接诱导ESR-1表达。利用X-Su(H)的一个DNA结合突变体,我们发现ESR-1的诱导需要X-Su(H)的活性。最后,在胚胎中表达该DNA结合突变体导致一种神经发生表型,同时X-Delta-1和XNGNR1(一种在初级神经发生过程中表达的神经源性基因)的表达也增加。这些结果表明,X-Su(H)的激活是非洲爪蟾胚胎初级神经发生过程中Notch信号通路的关键步骤。

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