p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development
p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development
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DOI：
10.1038/19539
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发表时间：
1999-04-22
期刊：
影响因子：
64.8
通讯作者：
McKeon, F
中科院分区：
文献类型：
--
作者：
Yang, A;Schweitzer, R;McKeon, F
P63基因是肿瘤抑制基因p53(参考文献1-5)的同源基因，在许多上皮组织的基底层或祖细胞层中高度表达(1)。在这里，我们报告了p63基因突变纯合子的小鼠在四肢、颅面和上皮组织发育方面存在重大缺陷。P63在肢芽、鳃弓和表皮附属物的外胚层表面表达，这些都是引导中胚层形态发生的相互信号部位。截肢是由于未能维持顶端外胚层脊，这是一种对肢体发育至关重要的复层上皮。p63(-/-)小鼠的胚胎表皮经历了一个不寻常的非再生分化过程，最终显著缺乏所有鳞状上皮及其衍生细胞，包括乳腺、泪腺和唾液腺。综上所述，我们的结果表明，p63对于维持维持上皮发育和形态发生所必需的前体细胞群至关重要。
The p63 gene, a homologue of the tumour-suppressor p53 (refs 1-5), is highly expressed in the basal or progenitor layers of many epithelial tissues(1). Here we report that mice homozygous for a disrupted p63 gene have major defects in their limb, craniofacial and epithelial development. p63 is expressed in the ectodermal surfaces of the limb buds, branchial arches and epidermal appendages, which are all sites of reciprocal signalling that direct morphogenetic patterning of the underlying mesoderm. The limb truncations are due to a failure to maintain the apical ectodermal ridge, a stratified epithelium, essential for Limb development The embryonic epidermis of p63(-/-) mice undergoes an unusual process of non-regenerative differentiation, culminating in a striking absence of all squamous epithelia and their derivatives, including mammary, lacrymal and salivary glands. Taken together, our results indicate that p63 is critical for maintaining the progenitor-cell populations that are necessary to sustain epithelial development and morphogenesis.