Wnt6 signaling regulates heart muscle development during organogenesis.

Mesodermal tissue with heart forming potential (cardiogenic mesoderm) is induced during gastrulation. This cardiogenic mesoderm later differentiates into heart muscle tissue (myocardium) and non-muscular heart tissue. Inhibition of Wnt/beta-catenin signaling is known to be required early for induction of cardiogenic mesoderm; however, the identity of the inhibiting Wnt signal itself is still elusive. We have identified Wnt6 in Xenopus as an endogenous Wnt signal, which is expressed in tissues close to and later inside the developing heart. Our loss-of-function experiments show that Wnt6 function is required in the embryo to prevent development of an abnormally large heart muscle. We find, however, that Wnt6 is not required as expected during gastrulation stages, but later during organogenesis stages just before cells of the cardiogenic mesoderm begin to differentiate into heart muscle (myocardium). Our gain-of-function experiments show that Wnt6 and also activated canonical Wnt/beta-catenin signaling are capable of restricting heart muscle development at these relatively late stages of development. This repressive role of Wnt signaling is mediated initially via repression of cardiogenic transcription factors, since reinstatement of GATA function can rescue expression of other cardiogenic transcription factors and downstream cardiomyogenic differentiation genes.

Wnt6 expression in epidermis and epithelial tissues during Xenopus organogenesis.

Here, we report the localization within embryonic tissues of xWnt6 protein; together with the temporal and spatial expression of Xenopus laevis Wnt6 mRNA. Wnt6 expression in Xenopus embryos is low until later stages of neurulation, when it is predominantly found in the surface ectoderm. Wnt6 expression increases during early organogenesis in the epidermis overlaying several developing organs, including the eye, heart, and pronephros. At later stages of development, Wnt6 mRNA and protein generally localize in epithelial tissues and specifically within the epithelial tissues of these developing organs. Wnt6 localization correlates closely with sites of both epithelial to mesenchymal transformations and mesenchymal to epithelial transformations. Xenopus Wnt6 sequence and its expression pattern are highly conserved with other vertebrates. Xenopus embryos, therefore, provide an excellent model system for investigating the function of vertebrate Wnt6 in organ development and regulation of tissue architecture.