The role of Sfrp and DKK proteins in cardiomyocyte development

In this review, we summarize the role of Wnt proteins in cardiomyogenesis. More specifically, we focus on how the development of cardiomyocytes from precursor cells involves a complex interplay between Wnt canonical β‐catenin signaling pathways and Wnt noncanonical signaling pathways involving PCP and JNK. We also describe recent literature which suggests that endogenous Wnt inhibitors such as the Sfrp and DKK proteins play important roles in regulating the cardiomyocyte differentiation.
Srfp2 mediates cardiomyocyte differentiation by inhibiting Wnt3a. Wnt3a is a canonical Wnt that activates b‐catenin and inhibits cardiac specification. In contrast, Wnt11 is a noncanonical Wnt, inhibits b‐catenin and promotes differentiation into cardiomyocytes. The addition of Sfrp2 upsets this balance as it binds, and sequesters, Wnt3a but not Wnt11; thereby leaving Wnt11 free to bind to Fzd5 and activate the noncanonical pathway resulting in cardiac differentiation.