p63 is a p53 homologue required for limb and epidermal morphogenesis

The p53 tumour suppressor is a transcription factor that regulates the prog ression of the cell through its cycle and cell death (apoptosis) in respons e to environmental stimuli such as DNA damage and hypoxia(1,2). Even though p53 modulates these critical cellular processes, mice that lack p53 are de velopmentally normal(3), suggesting that p53-related proteins might compens ate for the functions of p53 during embryogenesis. Two p53 homologues, p63 and p73, are known(4,5) and here we describe the function of p63 in vivo. M ice lacking p63 are born alive but have striking developmental defects. The ir limbs are absent or truncated, defects that are caused by a failure of t he apical ectodermal ridge to differentiate. The skin of p63-deficient mice does not progress past an early developmental stage: it lacks stratificati on and does not express differentiation markers. Structures dependent upon epidermal-mesenchymal interactions during embryonic development, such as ha ir follicles, teeth and mammary glands, are absent in p63-deficient mice. T hus, in contrast to p53, p63 is essential for several aspects of ectodermal differentiation during embryogenesis.