Mills A A, Zheng B, Wang X J, Vogel H, Roop D R, Bradley A
Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Nature. 1999 Apr 22;398(6729):708-13. doi: 10.1038/19531.
The p53 tumour suppressor is a transcription factor that regulates the progression of the cell through its cycle and cell death (apoptosis) in response to environmental stimuli such as DNA damage and hypoxia. Even though p53 modulates these critical cellular processes, mice that lack p53 are developmentally normal, suggesting that p53-related proteins might compensate for the functions of p53 during embryogenesis. Two p53 homologues, p63 and p73, are known and here we describe the function of p63 in vivo. Mice lacking p63 are born alive but have striking developmental defects. Their limbs are absent or truncated, defects that are caused by a failure of the apical ectodermal ridge to differentiate. The skin of p63-deficient mice does not progress past an early developmental stage: it lacks stratification and does not express differentiation markers. Structures dependent upon epidermal-mesenchymal interactions during embryonic development, such as hair follicles, teeth and mammary glands, are absent in p63-deficient mice. Thus, in contrast to p53, p63 is essential for several aspects of ectodermal differentiation during embryogenesis.
p53肿瘤抑制因子是一种转录因子，它能响应DNA损伤和缺氧等环境刺激，调节细胞周期进程和细胞死亡（凋亡）。尽管p53调节这些关键的细胞过程，但缺乏p53的小鼠在发育上是正常的，这表明p53相关蛋白可能在胚胎发生过程中补偿了p53的功能。已知有两种p53同源物，p63和p73，在这里我们描述p63在体内的功能。缺乏p63的小鼠出生时存活，但有明显的发育缺陷。它们的四肢缺失或截断，这些缺陷是由顶端外胚层嵴未能分化所致。p63缺陷小鼠的皮肤无法越过早期发育阶段：它缺乏分层，也不表达分化标志物。在胚胎发育过程中依赖于表皮-间充质相互作用的结构，如毛囊、牙齿和乳腺，在p63缺陷小鼠中不存在。因此，与p53不同，p63在胚胎发生过程中外胚层分化的几个方面是必不可少的。
