Regeneration, neural crest derivatives and retinoids: a new synthesis

Consideration of recent data from diverse fields of biology permits the presentation of a general theory to explain the underlying mechanism and phylogenetic distribution of vertebrate regenerative capacity. It is suggested that dermal xanthophores, which are neural crest derivatives that contain carotenoid pigments, serve as storage reservoirs for proretinoids. At trauma, carotenoids are released and are converted to retinoids. The spatial distribution of xanthophores at the amputation site determines the amount of carotenoids released, which in turn determines the number of cells which will participate in regeneration and their degree of dedifferentiation. It also influences the proliferative and morphogenetic potential of the blastema. The theory is based on several factors. (1) The pluripotency of neural crest derivatives in general and that of chromatophores in particular; (2) The storage metabolism of carotenoids, especially their convertability to retinoids; (3) The known roles of retinoids in regeneration; (4) Evidence suggesting a relationship between carotenoids and regeneration in invertebrates; and (5) Dynamic characteristics of regenerating systems. The theory is experimentally testable with currently available technology. Specific review of data concerning urodele lens regeneration illustrates the theory. Evidence from amphibian limb regeneration is also presented. Methods of evaluation of other regeneration systems are outlined.