Transient Nodal Signaling in Left Precursors Coordinates Opposed Asymmetries Shaping the Heart Loop
| Autor: | Jean-François Le Garrec, Sigolène M. Meilhac, Ségolène Bernheim, Audrey Desgrange, Tobias Holm Bønnelykke |
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| Přispěvatelé: | Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Morphogenèse du cœur - Heart morphogenesis (Imagine - Institut Pasteur U1163), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Collège Doctoral, Sorbonne Université (SU), This work was supported by core funding from the Institut Pasteur, state funding from the Agence Nationale de la Recherche under 'Investissementsd’avenir' program (ANR-10-IAHU-01), a grant from the ANR (16-CE17-0006-01) to S.M.M. and the MSD-Avenir fund (Devo-Decode project). A.D., S.B., and T.B. have benefited from a fellowship of the Fondation Lefoulon Delalande, the Société Française de Pédiatrie, and the Pasteur - Paris University (PPU) International PhD Program respectively, S.M.M. is an INSERM research scientist., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-16-CE17-0006,Heart_asymmetry,Asymétrie précoce requise pour l'alignement des chambres cardiaques : développement et pathologie(2016), CCSD, Accord Elsevier, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Asymétrie précoce requise pour l'alignement des chambres cardiaques : développement et pathologie - - Heart_asymmetry2016 - ANR-16-CE17-0006 - AAPG2016 - VALID, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Collège doctoral [Sorbonne universités] |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Heart morphogenesis
Cellular differentiation Nodal signaling Mesoderm Extracellular matrix Mice left-right asymmetry 0302 clinical medicine heart looping Heart looping Transgenes [SDV.BDD]Life Sciences [q-bio]/Development Biology Physics 0303 health sciences Effector left-right bias Cell Differentiation Heart congenital heart defects Extracellular Matrix Cell biology Signalling Signal Transduction Heart Defects Congenital Nodal Protein Morphogenesis Organogenesis Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences heart morphogenesis 3D imaging [SDV.BDD] Life Sciences [q-bio]/Development Biology Animals Computer Simulation Molecular Biology Body Patterning Cell Proliferation 030304 developmental biology LOOP (programming language) Myocardium Cell Biology heterotaxy second heart field Embryo Mammalian left-right patterning NODAL 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Developmental Cell Developmental Cell, 2020, 55 (4), pp.413-431.e6. ⟨10.1016/j.devcel.2020.10.008⟩ Developmental Cell, Elsevier, 2020, 55 (4), pp.413-431.e6. ⟨10.1016/j.devcel.2020.10.008⟩ |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2020.10.008⟩ |
| Popis: | SummaryThe secreted factor Nodal has been shown to be a major left determinant. Although it is associated with severe congenital heart defects, its role in heart morphogenesis has remained poorly understood. Here, we report that Nodal is transiently active in precursors of the mouse heart tube poles, before the morphological changes of heart 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 signalling, regulating asymmetries in cell proliferation, cell differentiation and extra-cellular matrix composition. Our work provides novel insight into how Nodal regulates asymmetric organogenesis. |
| Databáze: | OpenAIRE |
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