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

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. Using high-resolution 4D imaging, Kidokoro et al. identify two key cell behaviors shaping the early heart tube. They further show that left-specific Nodal signaling promotes these cell behaviors, thereby driving tissue-scale left-right asymmetry.

Automated summary

Using high-resolution live imaging of zebrafish embryos, this study investigates the cellular dynamics underlying early heart morphogenesis and identifies two key cell behaviors, cell rearrangement and cell shape change, in shaping the heart tube. Left cells exhibit higher activity in these behaviors, driving more rapid convergence of the left primordium and rotation of the heart tube. Loss of Nodal signaling abolishes these asymmetric cell behaviors and convergence of the left and right heart primordia.