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Retinoids and the control of pattern in regenerating limbs.

It has recently been discovered that, as well as having effects on cell division and differentiation, retinoids induce dramatic changes in the development of pattern in limbs. Local application of retinoic acid to the anterior side of chick limb buds causes anteroposterior mirror-imaging such that the limb has six digits instead of three. In Rana limb buds retinoids induce changes in both the anteroposterior and proximodistal axes. In regenerating axolotl limbs their effect is primarily on the proximodistal axis. These proximodistal effects result in the regeneration of a complete limb from distal amputation levels. Concentration effects, time effects and the relative efficacy of various retinoids have been established. Cellular changes observed include a stimulation of epidermal mucopolysaccharide production, inhibition of cell division, induction of cartilage matrix breakdown and a stimulation of fibronectin production by mesodermal cells. The relevance of each of these changes to pattern effects has been determined. Initial experiments on the cellular location of radiolabelled retinoic acid are described. It thus seems that retinoids can change the determination of developing cells, and once we know the molecular basis of retinoid action then we should also know how developing cells become specified to form particular cell types.