The role of retinoid-binding proteins in the generation of pattern in the developing limb, the regenerating limb and the nervous system

We summarise existing data and describe new information on the levels and distribution of cellular retinoic acid-binding protein (CRABP) and cellular retinolbinding protein (CRBP) in the regenerating axolotl limb, the developing chick limb bud and the nervous system of the chick embryo in the light of the known morphogenetic effects of retinoids on these systems. In the regenerating limb, levels of CRABP rise 3- to 4-fold during regeneration, peaking at the time when retinoic acid (RA) is most effective at causing pattern duplications. The levels of CRBP are low. The potency of various retinoids in causing pattern respecification correlates well with the ability of these compounds to bind to CRABP. In the chick limb bud, the levels of CRABP are high and the levels of CRBP are low. Again the binding of various retinoids to CRABP correlates well with their ability to cause pattern duplications. By immunocytochemistry, we show that CRABP is present at high levels in the progress zone of the limb bud and is distributed across the anteroposterior axis in a gradient with the high point at the anterior margin. In the chick embryo, CRABP levels are high and CRBP levels are low. By immunocytochemistry, CRABP is localised primarily to the developing nervous system, labelling cells and axons in the mantle layer of the neural tube. These become the neurons of the commissural system. Also sensory axons label intensely with CRABP whereas motor axons do not and in the mixed nerves at the brachial plexus sensory and motor components can be distinguished on this basis. In the neural tube, CRBP only stains the ventral floor plate. Since the ventral floor plate may be a source of chemoattractant for commissural axons, we suggest on the basis of these staining patterns that RA may fulfill this role and thus be involved morphogenetically in the developing nervous system.