In the mouse, disruption of the Planar Cell Polarity (PCP) pathway is associated with congenital heart defects including double outlet right ventricle (DORV). This severe malformation disrupts the double blood circulation because both the aorta and pulmonary artery are connected to the right ventricle. Yet, its embryonic origin has remained unclear. In the fly embryo, the PCP pathway coordinates cells in the plane of epithelia. Inactivation of the core PCP component Vangl2 in the mouse was shown to disrupt elongation of the outflow tract in the embryonic heart tube associated with incomplete heart looping. We now address the mechanisms of heart looping defects in mutants for VANGL2 and its effector SHROOM3. 3D quantifications of heart shape and of cell architecture in the field of heart precursors, suggest that OFT shortening is not the cause of heart looping defects. Our analyses also highlight a novel role of the PCP pathway in modulating cell rearrangements in the heart field epithelium, with no planar polarity of VANGL2. Overall, our work provides novel insights into the role of the PCP pathway during heart morphogenesis relevant to congenital heart defects.
Invited by Suzanne Faure-Dupuy, Alberto De la Iglesia and Hugo Barreto, as part of the Post-doc seminar series.
