title: Activin A and transforming growth factor-beta stimulate heart formation in axolotls but not rescue cardiac lethal mutants.
abstract: In the Mexican axolotl (salamander), Ambystoma mexicanum, a recessive cardiac lethal mutation causes an incomplete differentiation of the myocardium. Mutant hearts lack organized sarcomeric myofibrils and do not contract throughout their lengths. We have previously shown that RNA purified from normal anterior endoderm or from juvenile heart tissue is able to rescue mutant embryonic hearts in an in vitro organ culture system. Under these conditions as many as 55% of formerly quiescent mutant hearts initiate regular contractions within 48 hours. After earlier reports that transforming growth factor-beta 1 and, to a lesser extent, platelet-derived growth factor-BB could substitute for anterior endoderm as a promoter of cardiac mesodermal differentiation in normal axolotl embryos, we decided to examine the effect of growth factors in the cardiac mutant axolotl system. In one type of experiment, stage 35 mutant hearts were incubated in activin A, transforming growth factors-beta 1 or beta 2, platelet-derived growth factor, or epidermal growth factor, but no rescue of mutant hearts was achieved. Considering the possibility that growth factors would only be effective at earlier stages of development, we tested transforming growth factors-beta 1 and beta 5, and activin A on normal and mutant precardiac mesoderm explanted in the absence of endoderm at neurula stage 14. We found that, although these growth factors stimulated heart tube formation in both normal and mutant mesoderm explants, only normal explants contained contractile myocardial tissue. We hypothesize that transforming growth factor-beta superfamily peptides initiate a cascade of responses in mesoderm that result in both changes in cell shape (the basis for heart morphogenesis) and terminal myocardial cytodifferentiation. The cardiac lethal mutation appears to be deficient only in the latter process.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, State University of New York, Health Science Center at Syracuse 13210, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Mangiacapra
authors.forename: M E
authors.initials: ME
authors.lastname: Fransen
authors.forename: L F
authors.initials: LF
authors.lastname: Lemanski
mesh_terms: D028341:Activins; D000557:Ambystoma / Q000196:embryology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005804:Genes, Lethal / Q000502:physiology; D006321:Heart / Q000196:embryology*; D007265:Inhibins / Q000502:physiology*; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000166:cytology / Q000648:ultrastructure; D009924:Organ Culture Techniques; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D004815:Epidermal Growth Factor