TY - JOUR TI - A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics AU - Le Garrec, Jean-François AU - Domínguez, Jorge N AU - Desgrange, Audrey AU - Ivanovitch, Kenzo D AU - Raphaël, Etienne AU - Bangham, J Andrew AU - Torres, Miguel AU - Coen, Enrico AU - Mohun, Timothy J AU - Meilhac, Sigolène M A2 - Harvey, Richard P VL - 6 PY - 2017 DA - 2017/11/28 SP - e28951 C1 - eLife 2017;6:e28951 DO - 10.7554/eLife.28951 UR - https://doi.org/10.7554/eLife.28951 AB - 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. KW - left-right patterning KW - heart morphogenesis KW - computer modelling KW - 3D shape JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -