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© Research
Publication : Developmental cell

Transient Nodal Signaling in Left Precursors Coordinates Opposed Asymmetries Shaping the Heart Loop.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Developmental cell - 23 Nov 2020

Desgrange A, Le Garrec JF, Bernheim S, Bønnelykke TH, Meilhac SM,

Link to Pubmed [PMID] – 33171097

Link to DOI – S1534-5807(20)30798-X10.1016/j.devcel.2020.10.008

Dev Cell 2020 Nov; 55(4): 413-431.e6

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 conditional mutants, 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.