[Control of the positioning of the vertebrate limb axes during development]

Limbs are formed after a series of complex interactions between tissues derived from the embryonic layers (surface ectoderm and somatopleural mesoderm). Data at both cellular and molecular levels are numerous. The developing limb becomes thus one of the best known system in the field of developmental biology. The limb bud derives from numerous embryonic tissues (surface ectoderm, somatopleural mesoderm, neural crest cells, somites, hematopoietic cells deriving from the splanchnopleura that gives rise to the aortic buds). Multiple interactions take place between these tissues. So, the definitive shape of a structure could depend on only one of its component. For example, the muscular shape is not dependent on the origin of muscle fibers but on the origin of somatopleural cells. Superior (or anterior) and inferior (or posterior) limbs differ by their shape. Some genes expressed by only one of the limb are known but genes specifying the identity of the limbs are still totally unknown. Three axes develop during the formation of the limb buds: proximo-distal, antero-posterior and ventro-dorsal. The formation of the proximo-distal axis is due to the induction of the apical ectodermal ridge, a specialized region of the surface ectoderm in which cells are prismatic and associated by gap junctions. The family of secreted FGF and their receptors play a major role in the regulation of the development of this axis. Furthermore, some genes from Hox complexes a and d participate into the regulation of the positional identity along this axis. The antero-posterior axis is determined by the zone of polarizing activity that secretes Sonic hedgehog. This molecules fashions a gradient of concentration that differentiates the future antero-posterior derivatives. At last, the ventro-dorsal axis depends on the surface ectoderm that have received first positional informations from the mesoderm. The dorsal region is specified by Wnt7a and Lmx1 whereas Engrailed 1 gene plays a role in ventral specification.