Nodal signaling promotes the speed and directional movement of cardiomyocytes in zebrafish

Members of the Nodal family regulate left-right asymmetry during vertebrate organogenesis, but it is unclear how Nodal signaling controls asymmetric morphogenesis at the cellular level. We used high-resolution time-lapse imaging in zebrafish to compare the movements of cardiomyocytes in the presence or absence of Nodal signaling. Loss of Nodal signaling in late-zygotic mutants for the Nodal co-receptor one-eyed pinhead (LZoep) abolished the leftward movement of cardiomyocytes. Global heart rotation was blocked but cardiomyocyte neighbor relationships were maintained as in wild type. Cardiomyocytes in LZoep mutants moved more slowly and less directionally than their wild-type counterparts. The phenotypes observed in the absence of Nodal signaling strongly resemble abnormalities found in BMP signaling mutants. These results indicate that a Nodal-BMP signaling cascade drives left-right heart morphogenesis by regulating the speed and direction of cardiomyocyte movement.