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XB-ART-38433
Dev Biol November 15, 2008; 323 (2): 177-88.

Wnt6 signaling regulates heart muscle development during organogenesis.

Lavery DL , Martin J , Turnbull YD , Hoppler S .


Abstract
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.

PubMed ID: 18804460
PMC ID: PMC2593796
Article link: Dev Biol
Grant support: [+]

Species referenced: Xenopus
Genes referenced: gata4 gata6 myl2 nkx2-3 nkx2-5 tnni2 tnni3 wnt6
Morpholinos: wnt6 MO1 wnt6 MO2 wnt6 MO3


Article Images: [+] show captions
References [+] :
Afouda, GATA4, 5 and 6 mediate TGFbeta maintenance of endodermal gene expression in Xenopus embryos. 2005, Pubmed, Xenbase