[Regulation of the spatial organization of the regenerating extremity in amphibians]

Tests of the morphogenetic potency of the urodele limb regeneration blastema by a variety of transplantation experiments indicate that blastema is a self-organizing system. The cells of blastema inherit a memory of their position on the three cardinal axes of the limb. This memory is called positional memory, and it is fundamental to recognizing loss of structure, triggering cellular interactions to replace missing structures, and specifying the level from which new structures can begin. Retinoic acid (RA) modifies the positional memory in all three cardinal axes of the limb. The vitamin proximalizes positional memory in the proximodistal axis, posteriorizes it in the anteroposterior axis, and ventralizes it in the dorsoventral axis. In vivo and in vitro assays of interactions between cell derived from different proximodistal limb levels, before and after treatment with RA, suggest that the cellular basis of positional memory resides in recognition/affinity property of the cell surface. RA probably modifies positional memory by modulating transcription, via a nuclear retinoid receptor. It is suggested that the genes involved in specifying positional memory, and whose transcription is therefore affected in regenerating limbs, are homeo box genes and genes that encode for molecules involved in determining the composition and architecture of the cell surface and extracellular matrix.