A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics

Le Garrec, Jean-François, Domínguez, Jorge N, Desgrange, Audrey, Ivanovitch, Kenzo D, Raphaël, Etienne, Bangham, J Andrew, Torres, Miguel, Coen, Enrico, Mohun, Timothy J and Meilhac, Sigolène M (2017) A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics. eLife, 6. ISSN 2050-084X

[img]
Preview
PDF (Published manuscript) - Published Version
Available under License Creative Commons Attribution.

Download (7MB) | Preview

    Abstract

    How left-right patterning drives asymmetric morphogenesis is unclear. Here, we have quantified shape changes during mouse heart looping, from 3D reconstructions by HREM. In combination with cell labelling and computer simulations, we propose a novel model of heart looping. Buckling, when the cardiac tube grows between fixed poles, is modulated by the progressive breakdown of the dorsal mesocardium. We have identified sequential left-right asymmetries at the poles, which bias the buckling in opposite directions, thus leading to a helical shape. Our predictive model is useful to explore the parameter space generating shape variations. The role of the dorsal mesocardium was validated in Shh-/- mutants, which recapitulate heart shape changes expected from a persistent dorsal mesocardium. Our computer and quantitative tools provide novel insight into the mechanism of heart looping and the contribution of different factors, beyond the simple description of looping direction. This is relevant to congenital heart defects.

    Item Type: Article
    Faculty \ School: Faculty of Science > School of Computing Sciences
    Faculty of Science > School of Pharmacy
    Related URLs:
    Depositing User: Pure Connector
    Date Deposited: 05 Dec 2017 06:06
    Last Modified: 25 Jul 2018 14:21
    URI: https://ueaeprints.uea.ac.uk/id/eprint/65663
    DOI: 10.7554/eLife.28951

    Actions (login required)

    View Item