The p63 gene, a homologue of the tumour-suppressor p53, 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.

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

Mammary ductal elongation: differentiation of myoepithelium and basal lamina during branching morphogenesis.

Manifestation of the limb prepattern: limb development in the absence of sonic hedgehog function.

■ Abstract Vertebrate limb buds are embryonic structures for which much molecular and cellular data are known regarding the mechanisms that control pattern formation during development. Specialized regions of the developing limb bud, such as the zone of polarizing activity (ZPA), the apical ectodermal ridge (AER), and the non-ridge ectoderm, direct and coordinate the development of the limb bud along the anteriorposterior (AP), dorsal-ventral (DV), and proximal-distal (PD) axes, giving rise to a stereotyped pattern of elements well conserved among tetrapods. In recent years, specific gene functions have been shown to mediate the organizing and patterning activities of the ZPA, the AER, and the non-ridge ectoderm. The analysis of these gene functions has revealed the existence of complex interactions between signaling pathways operated by secreted factors of the HH, TGF-fl/BMP, WNT, and FGF superfamilies, which interact with many other genetic networks to control limb positioning, outgrowth, and patterning. The study of limb development has helped to establish paradigms for the analysis of pattern formation in many other embryonic structures and organs.

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Patterning Mechanisms Controlling Vertebrate Limb Development

Gap junctions are plasma membrane specializations characterized as aggregates of intramembranous particles in two apposed membranes meeting particle-to-particle in the 2–4 nm intermembrane ‘gap’. Recent thin-section and freeze-fracture evidence has revealed significant structural variations of gap junctional structure at various stages of development and from different organisms and tissues. It is suggested that a comparative analysis of these differences may provide clues to the specific biological function(s) of these ubiquitous organelles.

Structural diversity of gap junctions. A review.

Ultrastructural analysis of the apical ectodermal ridge during vertebrate limb morphogenesis. 1. the human forelimb with special reference to gap junctions.

Robert O. Kelley

Papers

Ultrastructural analysis of the apical ectodermal ridge during vertebrate limb morphogenesis. 1. the human forelimb with special reference to gap junctions.