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 highly expressed in the basal or progenitor layers of many epithelial tissues. Here we report that mice homozygous for a disrupted p63 gene have major defects in their limb, craniofacial and epithelial development. p63 is expresse...

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Bibliographic Details
Published in:Nature (London) 1999-04, Vol.398 (6729), p.714-718
Main Authors: McKeon, Frank, Yang, Annie, Schweitzer, Ronen, Sun, Deqin, Kaghad, Mourad, Walker, Nancy, Bronson, Roderick T, Tabin, Cliff, Sharpe, Arlene, Caput, Daniel, Crum, Christopher
Format: Article
Language:English
Subjects:
Animals
Body Patterning - genetics
Cell Differentiation - genetics
Craniofacial Abnormalities - genetics
Epidermis
Epidermis - embryology
Epidermis - growth & development
Epithelium - embryology
Epithelium - growth & development
Female
Fibroblast Growth Factor 8
Fibroblast Growth Factors - genetics
Forelimb - embryology
Forelimb - growth & development
Gene Expression
Gene Expression Regulation, Developmental
Gene Transfer Techniques
Genes
Hindlimb - embryology
Hindlimb - growth & development
Humanities and Social Sciences
letter
Limb Buds
Limb Deformities, Congenital - genetics
Male
Membrane Proteins
Mice
Mice, Inbred BALB C
Morphogenesis - genetics
multidisciplinary
Phosphoproteins - genetics
Prenatal development
Rodents
Science
Science (multidisciplinary)
Skull - embryology
Skull - growth & development
Trans-Activators
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Summary: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. 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.
ISSN:0028-0836
1476-4687
DOI:10.1038/19539