Key role of p63 in BMP-4-induced epidermal commitment of embryonic stem cells
Key role of p63 in BMP-4-induced epidermal commitment of embryonic stem cells
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DOI：
10.4161/cc.6.3.3800
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发表时间：
2007-02-01
期刊：
影响因子：
4.3
通讯作者：
Rouleau, Matthieu
中科院分区：
文献类型：
--
作者：
Aberdam, Daniel;Gambaro, Karen;Rouleau, Matthieu
在活体研究中，转基因和基因敲除小鼠已经证明p63亚型在外胚层和表皮发育中起着关键作用，但它们各自的功能仍然存在很大争议。由于胚胎干细胞可以分化为多种类型的细胞，它们是在体外概括胚胎发育的主要步骤的有效工具。我们最近报道了从小鼠ES细胞中有效地分化出外胚层和表皮细胞，并阐明了BMP-4在二元神经外胚层选择中的作用，它通过刺激SOX-1(+)神经前体细胞进行特异性凋亡，同时通过Delta Np63基因的激活诱导表皮分化。Delta Np63不是外胚层命运所必需的，但可以促进ES来源的外胚层细胞的增殖和表皮承诺。这一独特的细胞模型应该进一步为确定控制正常皮肤发育和p63-外胚层发育不良的分子机制提供一个强有力的工具。
In vivo studies, transgenic and knock-out mice have demonstrated that p63 isoforms play pivotal roles in ectodermal and epidermal development but their respective function remains highly controversial. Since embryonic stem (ES) cells can be differentiated into many cell types, they represent an effective tool to recapitulate in vitro the main steps of embryonic development. We recently reported the efficient derivation of ectodermal and epidermal cells from murine ES cells and clarified the function of BMP-4 in the binary neuroectodermal choice by stimulating sox-1(+) neural precursors to undergo specific apoptosis while inducing epidermal differentiation through Delta Np63 gene activation. Delta Np63 is not required for ectodermal fate but enhances ES-derived ectodermal cell proliferation and epidermal commitment. This unique cellular model should further provide a powerful tool for identifying the molecular mechanisms controlling normal skin development and in p63-ectodermal dysplasia human congenital pathologies.