The Wnt inhibitor Dkk1 is required for maintaining the normal cardiac differentiation program in Xenopus laevis

Abstract

Wnt proteins can activate different intracellular signaling pathways. These pathways need to be tightly regulated for proper cardiogenesis. The canonical Wnt/β-catenin inhibitor Dkk1 has been shown to be sufficient to trigger cardiogenesis in gain-of-function experiments performed in multiple model systems. Loss-of-function studies however did not reveal any fundamental function for Dkk1 during cardiogenesis. Using Xenopus laevis as a model we here show for the first time that Dkk1 is required for proper differentiation of cardiomyocytes, whereas specification of cardiomyocytes remains unaffected in absence of Dkk1. This effect is at least in part mediated through regulation of non-canonical Wnt signaling via Wnt11. In line with these observations we also found that Isl1, a critical regulator for specification of the common cardiac progenitor cell (CPC) population, acts upstream of Dkk1.

Ventricular, atrial, and outflow tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak

“…Jag1 is expressed anteriorly, complementary to the region where the cardiac crescent resides [ 47 ]. Dkk1 , a Wnt modulator controlling cardiac differentiation [ 48 , 49 ], was also enriched in clusters 2 and 3. Id 2 , a gene essential for the specification of the heart tube-forming progenitors [ 50 ] is also enriched in clusters 2 and 3.…”

Inhibition of Tet1- and Tet2-mediated DNA demethylation promotes immunomodulation of periodontal ligament stem cells

“…To investigate how Tet1/Tet2 regulate Wnt/β-catenin signaling, we examined the level of DKK-1, an upstream inhibitor of the WNT pathway 27 , and found that DKK-1 was downregulated in Tet1/Tet2 siRNA-treated PDLSCs. Immunofluorescence staining showed co-localization of DKK-1 with MSC surface marker CD146 (Fig.…”

Ventricular, atrial and outflow tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak

“…Jag1 is expressed anteriorly, complementary to the region where the cardiac crescent resides (Przemeck et al, 2003). Dkk1, a Wnt modulator controlling cardiac differentiation (David et al, 2008;Guo et al, 2019;Phillips et al, 2011), is also uniquely enriched in the right ventricle cluster. Id1 and 2, which are essential for the specification of the heart tube-forming progenitors (Cunningham et al, 2017) are enriched in both the left and right ventricle clusters but absent in the outflow and atrial clusters.…”