p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development

The p63 gene, a homologue of the tumour-suppressor p53 (refs 1-5), is highl y 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 d efects in their limb, craniofacial and epithelial development. p63 is expre ssed in the ectodermal surfaces of the limb buds, branchial arches and epid ermal appendages, which are all sites of reciprocal signalling that direct morphogenetic patterning of the underlying mesoderm. The limb truncations a re due to a failure to maintain the apical ectodermal ridge, a stratified e pithelium, essential for Limb development The embryonic epidermis of p63(-/ -) mice undergoes an unusual process of non-regenerative differentiation, c ulminating in a striking absence of all squamous epithelia and their deriva tives, 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 morpho genesis.