Principles of hand ontogenesis in man.

Human hand anlagen of different developmental stages are studied light and scanning electron microscopically. The findings are compared with experimental and ultrastructural results obtained from avian limb anlagen. Shaping, cell differentiation and the spatial arrangement of different cells are found to be the basic processes of hand development. The shaping of the arm and hand seems to anticipate future grasping movements. Factors controlling this developmental process are on the one hand the apical ectodermal ridge (AER) that maintains in the underlying mesoderm a high level of mitotic activity, and on the other hand a species-specific pattern of cell death in different zones of arm and hand. Interdigital cell death, microfilament bundles included in the basal compartment of AER cells, and local anchorings of the AER ectoderm by collagen fibrils are involved in finger separation. The flexion creases are genetically fixed and their development cannot be explained by mechanical factors. It is found that the early hand anlage is already composed of relatively autonomous founder cells committed to different lineages. This is true for the muscle precursor cells which originate from the brachial somites. These migrating somite cells are determined to belong to the myogenic lineage. However, their distribution, mitotic activity and later arrangement in single muscles are controlled by factors localized within the hand itself. Tendons develop autonomously from somatopleural cells. Other already committed cells are the angioblasts forming the endothelial lining of the blood vessels, the neural crest cells differentiating into melanocytes and Schwann cells, and the blood-derived cells like chrondro- or osteoclasts. The differentiation of somatopleural cells into cartilage, connective tissue or smooth muscle depends on their position within the hand anlage. Possible mechanisms leading to the specific pattern are discussed.