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

Autor:	Desgrange A; Université de Paris, Imagine - Institut Pasteur, Unit of Heart Morphogenesis, INSERM UMR1163, 75015 Paris, France., Le Garrec JF; Université de Paris, Imagine - Institut Pasteur, Unit of Heart Morphogenesis, INSERM UMR1163, 75015 Paris, France., Bernheim S; Université de Paris, Imagine - Institut Pasteur, Unit of Heart Morphogenesis, INSERM UMR1163, 75015 Paris, France., Bønnelykke TH; Université de Paris, Imagine - Institut Pasteur, Unit of Heart Morphogenesis, INSERM UMR1163, 75015 Paris, France; Sorbonne Université, Collège Doctoral, 75005 Paris, France., Meilhac SM; Université de Paris, Imagine - Institut Pasteur, Unit of Heart Morphogenesis, INSERM UMR1163, 75015 Paris, France. Electronic address: sigolene.meilhac@institutimagine.org.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2020 Nov 23; Vol. 55 (4), pp. 413-431.e6. Date of Electronic Publication: 2020 Nov 09.
DOI:	10.1016/j.devcel.2020.10.008
Abstrakt:	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. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020. Published by Elsevier Inc.)
Databáze:	MEDLINE
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