Biochemical Pathways Involved in the Respecification of Pattern by Retinoic Acid
We describe here experiments designed to further our understanding of the ways in which cells of the developing chick limb bud and the regenerating axolotl limb detect and respond to retinoids during the process of pattern respecification. The binding proteins for retinoic acid (CRABP) and retinol (CRBP) have been identified and quantified in the chick and axolotl. In an attempt to determine the role of CRABP the potency (ability to respecify pattern) of a range of retinoid analogues was correlated with their binding affinities to CRABP. Analogues that were inactive did not bind to CRABP and with the exception of one analogue, arotinoid, the converse was also true. Immunolocalisation of CRABP in the chick limb bud showed that it was concentrated in the progress zone at the tip of the limb and distributed in a graded form across the anteroposterior axis with the high point on the anterior side. Immunolocalisation of CRBP showed that it was restricted solely to the posterior side of the limb bud, the converse of CRABP. The relationship between these distributions and the endogenous gradient of retinoic acid is discussed. Finally, experiments on retinoic acid-induced changes in proteins, particularly protein phosphorylation are described and it is suggested that these may be casual in the respecification of pattern.
KeywordsRetinoic Acid Retinyl Palmitate Anteroposterior Axis Noic Acid Chick Limb
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