Retinoids Induce Duplications in Developing Vertebrate Limbs

Abstract

L imbs, including arms, legs, wings, and flippers, serve the wide variety of locomotion earmarking the lifestyle of vertebrate animals. Yet despite an astonishing diversity in form and size, all vertebrate limbs derive from a common plan (Owen 1849). The avian wing (Figure la) is a typical example of a forelimb. It starts proximally with the humerus, followed distally by radius/ulna and the handplate with digits. Limbs first arose in Devonian times (about 400 million years ago) when the lobe-finned fishes became land animals. Since then, basic limb morphology has been conserved. This suggests that development of the extremities during embryogenesis is essentially the same for all vertebrate animals. Indeed, all limbs arise as small buds in the early embryonic flank (Figure lb). Initially, the limb bud consists of an ectodermal jacket filled with mesenchymal tissue. During development, some of the mesenchymal cells differentiate into cartilage, bone, or muscle, and other cells undergo programmed cell death. Cell differentiation is coordinated: particular structures always arise at a predictable location and time, thus leading to the intricate pattern of a vertebrate limb. Young limb buds can readily be