BMP and FGF regulate the differentiation of multipotential pericardial mesoderm into the myocardial or epicardial lineage

Abstract

Proepicardial cells give rise to epicardium, coronary vasculature and cardiac fibroblasts. The proepicardium is derived from the mesodermal lining of the prospective pericardial cavity that simultaneously contributes myocardium to the venous pole of the elongating primitive heart tube. Using proepicardial explant cultures, we show that proepicardial cells have the potential to differentiate into cardiac muscle cells, reflecting the multipotency of this pericardial mesoderm. The differentiation into the myocardial or epicardial lineage is mediated by the cooperative action of BMP and FGF signaling. BMP2 is expressed in the distal IFT myocardium and stimulates cardiomyocyte formation. FGF2 is expressed in the proepicardium and stimulates differentiation into the epicardial lineage. In the base of the proepicardium, coexpression of BMP2 and FGF2 inhibits both myocardial and epicardial differentiation. We conclude that the epicardial/myocardial lineage decisions are mediated by an extrinsic, inductive mechanism, which is determined by the position of the cells in the pericardial mesoderm.

β-Catenin downregulation attenuates ischemic cardiac remodeling through enhanced resident precursor cell differentiation

“…This population was identified in the endo-and epicardial compartment resembling the localization of tissue-resident cardiac precursors already described in zebrafish (22). Similarly, subepicardial and subendocardial cardiac precursor cells have been identified in mammalian cardiac development (23,24).…”

Role of fibroblast growth factor signaling during proepicardium formation in the chick embryo

“…Nascent myocardial and proepicardial cells co-express marker genes of mesothelial cells and cardiac myocytes (Kruithof et al, 2006;Schlueter et al, 2006). Moreover, DiI (1,1 0 , di-octadecyl-3,3,3 0 ,3 0 ,-tetramethylindo-carbocyanine perchlorate) labeling experiments are consistent with a common origin of both cell populations from the lateral plate mesoderm (van Wijk et al, 2009).…”

“…Moreover, DiI (1,1 0 , di-octadecyl-3,3,3 0 ,3 0 ,-tetramethylindo-carbocyanine perchlorate) labeling experiments are consistent with a common origin of both cell populations from the lateral plate mesoderm (van Wijk et al, 2009). A common origin is also suggested by the ability of proepicardial explants to undergo cardiac myocyte differentiation in vitro (Kruithof et al, 2006;Schlueter et al, 2006). The exact mechanism that induces PE formation at the venous pole region is currently unknown.…”

The Arterial Epicardium: A Developmental Approach to Cardiac Disease and Repair

“…However, based on interaction between BMP and FGF, some of the progenitors of cardiomyocytes in the SHF share the same markers with cells in the underlying mesoderm of the SHF and the epicardial population [14]. Other data, including quail-chicken chimera, also do not support EPDC-cardiomyocyte transition [3].…”