A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics
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- Jean-François Le Garrec
- <italic>Imagine</italic> - Institut Pasteur, Laboratory of Heart Morphogenesis, Paris, France
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- Jorge N Domínguez
- Department of Experimental Biology, University of Jaén, CU Las Lagunillas, Jaén, Spain
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- Audrey Desgrange
- <italic>Imagine</italic> - Institut Pasteur, Laboratory of Heart Morphogenesis, Paris, France
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- Kenzo D Ivanovitch
- Cardiovascular Development Program, Centro Nacional de Investigaciones Cardiovasculares, CNIC, Madrid, Spain
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- Etienne Raphaël
- <italic>Imagine</italic> - Institut Pasteur, Laboratory of Heart Morphogenesis, Paris, France
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- J Andrew Bangham
- University of East Anglia, Norwich, United Kingdom
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- Miguel Torres
- Cardiovascular Development Program, Centro Nacional de Investigaciones Cardiovasculares, CNIC, Madrid, Spain
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- Enrico Coen
- John Innes Centre, Norwich Research Park, Norwich, United Kingdom
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- Timothy J Mohun
- The Francis Crick Institute, London, United Kingdom
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- Sigolène M Meilhac
- <italic>Imagine</italic> - Institut Pasteur, Laboratory of Heart Morphogenesis, Paris, France
抄録
<jats:p>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.</jats:p>
収録刊行物
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- eLife
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eLife 6 e28951-, 2017-11-28
eLife Sciences Publications, Ltd