Journal
DEVELOPMENTAL CELL
Volume 55, Issue 4, Pages 413-+Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2020.10.008
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Funding
- Institut Pasteur
- Agence Nationale de la Recherche under Investissementsd'avenir'' program [ANR-10-IAHU-01]
- ANR [16-CE17-0006-01]
- MSD-Avenir fund (DevoDecode project)
- Fondation Lefoulon Delalande
- Societe Francaise de Pediatrie
- Pasteur -Paris University (PPU) International PhD Program
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The secreted factor Nodal, known as a major left determinant, is associated with severe heart defects. Yet, it has been unclear how it regulates asymmetric morphogenesis such as heart looping, which align cardiac chambers to establish the double blood circulation. Here, we report that Nodal is transiently active in precursors of the mouse heart tube poles, before looping. In conditionalmutants, we show that Nodal is not required to initiate asymmetric morphogenesis. We provide evidence of a heart-specific random generator of asymmetry that is independent of Nodal. Using 3D quantifications and simulations, we demonstrate that Nodal functions as a bias of this mechanism: it is required to amplify and coordinate opposed left-right asymmetries at the heart tube poles, thus generating a robust helical shape. We identify downstream effectors of Nodal signaling, regulating asymmetries in cell proliferation, differentiation, and extracellular matrix composition. Our study uncovers how Nodal regulates asymmetric organogenesis.
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