Abstract
The limb develops from a small bud of undifferentiated mesenchyme cells encased in ectodermal epithelium. The mesenchyme cells give rise to the musculoskeletal system and the dermis, the ectoderm to the epidermis. Formation of the precise arrangement of differentiated cells and tissues depends on complex cell–cell interactions. Interactions between the apical ectodermal ridge and the underlying mesenchyme control limb bud outgrowth which is accompanied by formation of structures along the proximodistal axis, the zone of polarizing activity controls the craniocaudal axis and the surface ectoderm the dorsoventral axis. There has been considerable progress in identifying the genetic basis of limb development in model organisms and often the same genes have been found to be responsible for human congenital limb defects. Skeletal elements develop from condensations of mesenchyme cells which differentiate into cartilage rudiments that then ossify. Joints develop from inter-zonal mesenchyme between cartilage rudiments. Myogenic cells originate in the somites and migrate into the limb bud to form dorsal and ventral premuscle masses that split to generate the individual muscles. Limb endothelial cells are also of somitic origin and assemble into a vascular network that then remodels. Embryonic movements are vital for musculoskeletal development including joint cavitation.
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