The role of Sfrp and DKK proteins in cardiomyocyte development

Abstract

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.

Keywords: DKK; Sfrp2; cardiomyocyte.

Figure 1

Wnt signaling pathway. Wnt proteins signal via three pathways. The first pathway is known as the canonical β‐catenin pathway. There are also two noncanonical Wnt signaling pathways; the planar cell polarity (PCP) pathway and the Ca²+ pathway

Figure 2

Role of β‐catenin in cardiomyocyte differentiation. Activation of β ‐catenin in mesoderm cells is necessary to generate cardiac progenitors. Subsequent differentiation of these cardiac progenitors into cardiomyocytes requires β‐catenin inhibition

Figure 3

Srfp2 mediates cardiomyocyte differentiation by inhibiting Wnt3a. Undifferentiated cells express both Wnt3a and Wnt11. Wnt3a is a canonical Wnt that activates β‐catenin and inhibits cardiac specification. In contrast, Wnt11 is a noncanonical Wnt, inhibits β‐catenin and promotes differentiation into cardiomyocytes. The competing roles of Wnt3 and Wnt11 prevent cardiomyocyte differentiation. 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 non‐canonical pathway resulting in cardiac differentiation