VANGL2 shapes the mouse heart tube from adjacent epithelia and without planar polarity

Abstract

Disruption of the core Planar Cell Polarity component VANGL2 in mice is associated with congenital heart defects and impaired morphogenesis of the embryonic heart tube. However, the underlying mechanisms have remained unclear. Here we quantified in 3D the heart geometry and adjacent tissue architecture in a series of mutants to reveal a dual role of Vangl2 in shaping the heart tube. Together with cell labelling in the chick, we show that VANGL2 in multicellular junctions promotes second heart field cell rearrangements and thus the elongation of the arterial pole. In addition, apically localised VANGL2 and its downstream actin-binding effector SHROOM3 control the bilateral symmetry of the splanchnic mesoderm caudal to the venous pole. Disorganisation of this midline anchor is associated with a rotation of the heart tube and abnormal left ventricle position. Our work overall uncovers novel specific epithelial roles of VANGL2 unrelated to planar polarity during heart morphogenesis.