ZPA, Sonic Hedgehog gradient, and digit specification in the developing limb bud
The vertebrate limb bud is patterned along three axes by three organizers. The Zone of Polarizing Activity (ZPA) at the posterior margin secretes Sonic Hedgehog (SHH), a morphogen that specifies digit identity in a concentration-dependent manner (digit 5 → 4 → 3 → 2 from posterior to anterior). The Apical Ectodermal Ridge (AER) produces FGFs that maintain the progress zone — a proliferative region beneath the AER from which cells emerge and are permanently specified by their SHH exposure history. BMP signaling drives interdigital apoptosis to sculpt the hand. Grafting an ectopic ZPA to the anterior margin causes mirror-image digit duplications, a classical experiment demonstrating positional information.