|| Checking for direct PDF access through Ovid
As a universal means of communication and a critical tool for survival, the human hand is of extraordinary importance to our evolutionary survival. As the product of countless overlapping chemical signals, the upper extremity is highly dependent on a multifactoral web of genetic and environmental factors. At the molecular level, specialized signaling centers guide limb development along 3 spatial limb axes: (1) proximodistal, (2) anteroposterior, and (3) dorsoventral. Within the growing limb bud, the 3 main signaling centers are (1) the apical ectodermal ridge, (2) the zone of polarizing activity, and (3) the nonridge ectoderm. Cells within these signaling centers govern the process of limb differentiation via secretion of various chemical messengers. Although each aspect of extremity growth seems directly dependent on a process-specific mechanism, overall limb development relies on the proper interaction of these countless protein factors. Here, we review the macroscopic development of the upper limb and discuss the complex mechanisms underlying differentiation of the human hand.