The development of the vertebrate limb.

Knowledge of the early development of the tetrapod limb largely rests on studies conducted on the chick embryo, the main object of descriptive and experimental work on limb morphogenesis for the last 40 years. A short account is given here of the origin and gradual changes in size and shape of the limb bud, the structure of its ectodermal and mesodermal components, and the mechanisms at play during the early phases of the organogenesis of the skeletal pieces, joints, and muscles. From studies on the causality of limb morphogenesis in both amphibian and avian embryos, it appears that the mesodermal component of the primitive limb area, activated by influences exerted by the adjacent somitic mesoderm, is the primary seat of the limb developmental potencies. The limb type, the establishment of the limb axes, and the individuation, determination, and differentiation of the limb articles in a definite temporal sequence according to an orderly proximodistal pattern seem to be inherent properties of the mesoderm. Uncertainties exist as to (1) the nature of interactions between mesoderm and ectoderm in limb-bud outgrowth and pattern formation and (2) the precise role(s) played by the ectoderm, particularly by its apical thickening--a structure that, after all, does not form in urodeles and some anurans. Mention is also made of the regulation ability of chick limb-bud and of recent attempts to stimulate limb regeneration in mammals.