Limbs begin to form relatively late in development compared to the rest of the skeletal system, stimulated by a poorly understood initiation mechanism probably involving localized secretion of fibroblast growth factor-8 from an unknown origin. Retinoic acid acts locally in this process as well, and its inhibition leads to failure of limb formation. [A]

The mesenchyme of the limb bud consists of cells migrating from many locations in the embryo, each giving rise to a specific type of structure necessary for limb sensation and locomotion. The skeletal elements arise from the somatic mesoderm of the lateral plate (shown on right), which contributes to much of the limb bud mesenchyme. Initially, however, the mesenchyme of the limb bud consists solely of this lateral plate origin. As the basic skeletal plan is layed out, mesenchymal cells from the somites migrate in to form muscle cells, and neural crest cells migrate in to form both nerves and pigment cells. [A]

It is worth noting that the appendicular skeleton has a different embryonic origin than the axial skeleton and is not simply an extension of that skeleton but rather an entirely different system that is loosely connected through soft tissue such as muscles.