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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. [ABSTRACT FROM AUTHOR]

Patterning of the mouse embryo along the anteroposterior axis during body plan development requires migration of the distal visceral endoderm (DVE) towards the future anterior side by a mechanism that has remained unknown. Here we show that Nodal signalling and the regionalization of its antagonists are required for normal migration of the DVE. Whereas Nodal signalling provides the driving force for DVE migration by stimulating the proliferation of visceral endoderm cells, the antagonists Lefty1 and Cerl determine the direction of migration by asymmetrically inhibiting Nodal activity on the future anterior side. [ABSTRACT FROM AUTHOR]

Reports on the discovery of a new gene located at the inversion of embryonic turning (inv) locus. How most vertebrate internal organs show a distinctive left/right asymmetry; Expression of the gene seen as being the highest in the kidneys and liver among adult tissues, and is seen in presomite-stage embryos; Findings suggesting that transgenic introduction of a minigene encoding the candidate protein restores normal left/right asymmetry and kidney development in the inv mutant.

Describes a member of the transforming growth factor-beta family called the lefty gene which may encode a morphogen for L-R determination. Examples of lateral asymmetry in vertebrates; Molecular mechanism governing the establishment of left-right handedness; Expression of the lefty gene in the left half of gastrulating mouse embryos; Period of appearance.

Presents a study that described the development of a system in which mouse embryos are cultured under an artificial fluid flow. Relation between the direction of the intrinsic nodal flow and that of the pump-driven artificial flow; Reversal of the intrinsic nodal flow by fast rightward artificial flow; Reversal of situs of wild-type embryos at the presomite stage by fast rightward flow.

The generation of morphological, such as left?right, asymmetry during development is an integral part of the establishment of a body plan. Until recently, the molecular basis of left?right asymmetry was a mystery, but studies indicate that Nodal and the Lefty proteins, transforming growth factor-β-related molecules, have a central role in generating asymmetric signals. Although the initial mechanism of symmetry breaking remains unknown, developmental biologists are beginning to analyse the pathway that leads to left?right asymmetry establishment and maintenance. [ABSTRACT FROM AUTHOR]