Nodal signaling regulates asymmetric cellular behaviors, driving clockwise rotation of the heart tube in zebrafish

Abstract

Clockwise rotation of the primitive heart tube, a process regulated by restricted left-sided Nodal signaling, is the first morphological manifestation of left-right asymmetry. How Nodal regulates cell behaviors to drive asymmetric morphogenesis remains poorly understood. Here, using high-resolution live imaging of zebrafish embryos, we simultaneously visualized cellular dynamics underlying early heart morphogenesis and resulting changes in tissue shape, to identify two key cell behaviors: cell rearrangement and cell shape change, which convert initially flat heart primordia into a tube through convergent extension. Interestingly, left cells were more active in these behaviors than right cells, driving more rapid convergence of the left primordium, and thereby rotating the heart tube. Loss of Nodal signaling abolished the asymmetric cell behaviors as well as the asymmetric convergence of the left and right heart primordia. Collectively, our results demonstrate that Nodal signaling regulates the magnitude of morphological changes by acting on basic cellular behaviors underlying heart tube formation, driving asymmetric deformation and rotation of the heart tube.