Stage dependent effects of retinoids on the development and regeneration of limbs in amphibians

Excess of vitamin A and its derivatives (retinoids) produces severe teratogenic effects on limb development in mammalian embryos and in amphibians. In both, such effects are dependent on the stage of the developing limbs and the state of differentiation of their cells when the retinoid is adiminstered during their ontogenesis. In the regenerating limbs of amphibians, however, retinoids produce a radical promotional effect on the regeneration by increasing the developmental potency of the cells of the regeneration blastema which may then forms not only the limb part actually removed distal to the level of amputation but also one or more limb structures proximal to it. Thus some or all parts of the stump are serially duplicated in the regenerates. Studies on anuran tadpoles and urodeles have shown that such effect termed proximalization of the blastema also depends on when the retinoid is administered after limb amputation during the formation, growth, morphogensis and histogenesis of the blastema. The most proximalized regenerates are obtained when the retinoid is given at early bud stage of the blastema when its cells are in the phase of dedifferentiation ; the effect is progressively reduced with exposure to the retinoid at later developmental stages of the blastema becoming zero with the onset of redifferentiation.