Differential requirement for the dual functions of β-catenin in embryonic stem cell self-renewal and germ layer formation.
Differential requirement for the dual functions of β-catenin in embryonic stem cell self-renewal and germ layer formation.
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DOI：
10.1038/ncb2260
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发表时间：
2011-06-19
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
经典Wnt信号转导与小鼠和人类胚胎干细胞（ESC）的维持有关，但其要求存在争议。β-连环蛋白是这种高度保守的Wnt通路中的关键组分，充当转录反式激活因子。然而，β-连环蛋白在调节细胞-细胞粘附的质膜上具有额外的作用，使得缺乏β-连环蛋白的细胞/组织的分析复杂化。我们在此报道了β-catenin缺陷小鼠ESC（mESC）系的产生，并表明在β-catenin缺乏的情况下自我更新得以维持。斑珠蛋白上调部分挽救了细胞粘附，但在分化过程中未能维持。当分化为聚集体时，野生型mESC形成所有三个胚层的后代，而β-连环蛋白缺陷型mESC中的中内胚层胚层形成和神经元分化是缺陷的。Tcf/Lef-signaling缺陷的β-catenin变体重建钙粘蛋白介导的细胞粘附，拯救定形内胚层和神经上皮形成，表明β-catenin细胞粘附功能比其信号传导功能对这些过程更重要。
Canonical Wnt-signalling has been implicated in mouse and human embryonic stem cell (ESC) maintenance, however its requirement is controversial. β-catenin is the key component in this highly conserved Wnt pathway, acting as a transcriptional transactivator. Yet, β-catenin has additional roles at the plasma membrane regulating cell-cell adhesion, complicating the analyses of cells/tissues lacking β-catenin. We report here the generation of a β-catenin deficient mouse ESC (mESC) line and show that self-renewal is maintained in absence of β-catenin. Cell-adhesion is partially rescued by plakoglobin up-regulation, but fails to be maintained during differentiation. When differentiated as aggregates, wild-type mESCs form descendents of all three germ layers, while mesendodermal germ layer formation and neuronal differentiation are defective in β-catenin deficient mESCs. A Tcf/Lef-signalling defective β-catenin variant, which re-establishes cadherin-mediated cell-adhesion, rescues definitive endoderm and neuroepithelial formation, suggesting that β-catenin cell-adhesion function is more important than its signalling function for these processes.
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