IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis

This study reports a function for IGFBP-4 as a cardiogenic growth factor, showing that IGFBP-4 enhances cardiomyocyte differentiation in vitro, and knockdown of IGFBP-4 attenuated cardiomyogenesis both in vitro and in vivo. The effect was independent of IGF binding, and was mediated by canonical Wnt signalling. IGFBP-4 physically interacted with a Wnt receptor Frizzled 8 (Frz8) and a Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6), and inhibited Wnt3A binding to Frz8 and LRP6.