The mesodermal source of fibronectin is required for heart morphogenesis and cardiac outflow tract elongation by regulating cell shape, polarity, and mechanotransduction in the second heart field

Abstract

Failure in the elongation of the cardiac outflow tract results in congenital heart disease due to ventricular septum defects and misalignment of the great vessels. The cardiac outflow tract lengthens by the accretion of progenitors derived from the second heart field (SHF). SHF cells in the splanchnic mesoderm are exquisitely organized into an epithelial-like layer forming the dorsal pericardial wall (DPW). Tissue tension within the DPW, cell polarity, and proliferation, are requisite for the addition of SHF-derived cells to the heart and outflow tract elongation. However, genes regulating these processes are not completely understood. Using conditional mutagenesis in the mouse, we show that Fn1 synthesized by the SHF is a central regulator of the epithelial architecture in the DPW. Fn1 expression is enriched in the anterior DPW and mediates outflow tract elongation by regulating cell polarity, shape, cohesion, and mechanotransduction. Our studies establish that Fn1 synthesized specifically by the mesoderm coordinates multiple cellular behaviors in the anterior DPW requisite for the elongation of the cardiac outflow tract and embryonic viability.