Reaction-diffusion control of heart development: evidence for activation and inhibition in precardiac mesoderm

In axolotl embryos homozygous for the cardiac-lethal (c) gene, the heart never begins to beat. Recently, we demonstrated that the c gene affects the heart mesoderm directly, making the latter incapable of responding to normal inductive stimuli. Based on these results, we proposed that a reaction-diffusion mechanism controls the later stages of vertebrate cardiogenesis. In the present study, we use a series of transplantations to examine the precardiac mesoderm of wild-type and cardiac-lethal mutant axolotl embryos for the activation and inhibition predicted by our model. When one or both heart primordia in c/c embryos were replaced with +/+ tissue at early stages, functional hearts developed, indicating that an activator-like activity is present in wild-type heart mesoderm. At later stages, replacement of the entire heart-field mesoderm also rescued mutant embryos, but replacement of only the heart-forming mesoderm did not, indicating that the mutant heart field has inhibitory properties. These results demonstrate that activator- and inhibitor-like factors are present in pre-cardiac mesoderm and thus provide evidence for reaction-diffusion control of postinductive heart development.