ABSTRACT
Allopurinol, a drug that inhibits the enzyme xanthine dehydrogenase (XDH), is known to cause hypermelanism in the axolotl. The hypermelanistic condition that results from allopurinol treatment is similar in most respects to the phenotype that results from the action of the melanoid (m) gene in axolotls. On the basis of structural and biochemical studies, it now seems clear that genetic and drug-induced hypermelanism are the same in the following ways. 1) Both types of melanism result in the production of more than normal amounts of melanin and more melanin-containing cells (melanophores). 2) In both cases the amount of pteridine-associated yellow pigment declines during development, and this is associated directly with fine structural changes that occur within the pigment organelles (pterinosomes) of yellow pigment cells (xanthophores). 3) In both cases the hypermelanistic condition results in the suppression of reflecting pigment cell (iridophore) differentiation. 4) Both conditions have now been linked directly to depressed levels of XDH activity. Thus both genetic and drug-induced hypermelanism result in alterations in the normal differentiation of all three pigment cell types and the subsequent disruption of normal pigment pattern formation. The possible significance of these findings with regard to factors known or suspected to direct the migration and/or differentiation of neural crest-derived pigment cells is discussed.
Subject(s)
Allopurinol/pharmacology , Ambystoma mexicanum/genetics , Ambystoma/genetics , Chromatophores/metabolism , Melanins/metabolism , Animals , Cell Differentiation/drug effects , Chromatophores/cytology , Chromatophores/ultrastructure , Metabolic Diseases/chemically induced , Metabolic Diseases/genetics , Microscopy, Electron , Xanthine Dehydrogenase/deficiency , Xanthine Dehydrogenase/metabolismABSTRACT
Guanosine is shown to dramatically alter the pigment phenotype of axolotls by suppressing melanization and enhancing the biosynthesis and deposition of purine-derived pigments. Phenotypic changes caused by guanosine are manifested by altered chromatophore differentiation patterns such that few black pigment cells (melanophores) differentiate (and those that do are punctate and necrotic in appearance), whereas the development of yellow (xanthophore) and reflecting (iridophore) pigment cells is enhanced. Mechanisms for changes in chromatophore differentiation, and thus pattern formation, are discussed, including the possibility that pigment cells may undergo transdifferentiation in vivo.
