“…Indeed, like tooth development limb development involves and depends on reciprocal epithelial-mesenchymal interactions, polarized growth, mesenchymal condensations, proliferation of specific cell populations, and establishment of multi-axis symmetries. In the developing limb, two specialized areas, the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA), exert key roles in development (reviewed by Ide, 1990;Tabin, 1991). In particular, the ZPA, a small group of cells located at the posterior margin of the limb, acts as a source of signalling factors, such as Sonic hedgehog (Shh), and determines the antero-posterior axis of the limb (Riddle et al, 1993).…”