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XB-ART-46774
Development April 1, 2013; 140 (7): 1537-49.

sfrp1 promotes cardiomyocyte differentiation in Xenopus via negative-feedback regulation of Wnt signalling.

Gibb N , Lavery DL , Hoppler S .


Abstract
Wnt signalling is a key regulator of vertebrate heart development, yet it is unclear which specific Wnt signalling components are required to regulate which aspect of cardiogenesis. Previously, we identified Wnt6 as an endogenous Wnt ligand required for controlling heart muscle differentiation via canonical Wnt/β-catenin signalling. Here we show for the first time a requirement for an endogenous Wnt signalling inhibitor for normal heart muscle differentiation. Expression of sfrp1 is strongly induced in differentiating heart muscle. We show that sfrp1 is not only able to promote heart muscle differentiation but is also required for the formation of normal size heart muscle in the embryo. sfrp1 is functionally able to inhibit Wnt6 signalling and its requirement during heart development relates to relieving the cardiogenesis-restricting function of endogenous wnt6. In turn, we discover that sfrp1 expression in the heart is regulated by Wnt6 signalling, which for the first time indicates that sfrp genes can function as part of a Wnt negative-feedback regulatory loop. Our experiments indicate that sfrp1 controls the size of the differentiating heart muscle primarily by regulating cell fate within the cardiac mesoderm between muscular and non-muscular cell lineages. The cardiac mesoderm is therefore not passively patterned by signals from the surrounding tissue, but regulates its differentiation into muscular and non-muscular tissue using positional information from the surrounding tissue. This regulatory network might ensure that Wnt activation enables expansion and migration of cardiac progenitors, followed by Wnt inhibition permitting cardiomyocyte differentiation.

PubMed ID: 23482489
PMC ID: PMC4074298
Article link: Development
Grant support: [+]
Genes referenced: bmp4 fzd7 gal.2 gata4 gata5 gata6 grn isl1 myl2 nkx2-5 odc1 pcna sfrp1 tbx2 tnni3 wnt6
Antibodies: Mapk1 Ab9 Sfrp1 Ab1
Morpholinos: gata4 MO2 gata4 MO3 gata5 MO3 gata6 MO1 gata6 MO2 sfrp1 MO1 sfrp1 MO2 wnt6 MO3


Article Images: [+] show captions
References:
Afouda, 2008, Pubmed, Xenbase [+]


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