Stages of development

The stages of development of the limb bud are very stereotyped. It first appears around the 26th day of gestation as a mass of proliferating mesoderm beneath a thickened epithelial layer - the apical ectodermal ridge (AER). The mesodermal core is derived from the somatic layer of lateral plate mesoderm; it goes on to form the bones and connective tissue of the limb. Soon afterwards, spinal nerves grow into the bud and the AER induces development in a proximal to distal axis. A capillary network forms within the mesoderm and these fine vessels soon merge to form a main stem artery along the axis of the limb bud. This drains into a marginal vein.

By the fifth week of development, a paddle shaped hand (handplate) has formed. An equivalent process occurs in the caudal limb buds to form footplates. The hand and footplates are separated from the rest of the limb by a circular constriciton. Precursor cartilage structures form within the mesoderm at the site of future skeletal elements. Joints begin to form by the condensation of chondrocyte precursors as dense plates of cartilage. Myoblasts migrate into the bud and form both dorsal and ventral muscle masses.

By the sixth week, digital rays begin to be appreciated as a result of apoptotic cell death within the interspaces. As the mesenchyme elongates and differentiates further within the seventh week, the whole limb bud externally rotates 90 degrees relative to the body to bring the future palm into an anatomical position with the extensor muscles on the lateral and posterior surface. Joint differentiation progresses with cavitation at the sites of cartilage differentation; further development requires motion for remodelling of future articular surfaces.

Bone begins to form from the cartilaginous precursor by the twelfth week of development. This is seen as primary ossification centers present within all the long bones. Usually, endochondral ossification commences from the diaphysis of a long bone and progresses with time to the opposite ends of the bone. At birth, the diaphysis is completely ossified whereas the two extremities - the epiphyses - remain cartilaginous. Subsequently, new ossification centers arise in the epiphyses. The cartilage intervening between the ephiphyses and the diaphysis is termed the epiphyseal plate. Long bones have two epiphyseal plates whereas small bones such as the phalanges usually have one.

Radiolographic examination of the ossification centers of bones in the hand and wrist is used to assess the extent of skeletal maturity. Similar information can be gathered about fetal maturation by ultrasonography of fetal bones.