1. Departments of Cell Biology
2. Genetics, Harvard Medical School,
3. Immunology Research Division
4. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
5. Sanofi Biorecherche, Innopole BP 137, 31676 Labege Cedex, France
6. US Department of Agriculture, Human Nutrition Research Center on Aging, and Department of Pathology, Tufts University School of Veterinary Medicine, Boston, Massachusetts 02111, USA

Correspondence to: Frank McKeon¹ Correspondence and requests for materials should be addressed to F.McK. (e-mail: Email: frank_mckeon@hms.harvard.edu).

Abstract

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 tissues¹. 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.