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Elife. 2017 Nov 28;6. pii: e28951. doi: 10.7554/eLife.28951.

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

Author information

1
<italic>Imagine</italic> - Institut Pasteur, Laboratory of Heart Morphogenesis, Paris, France.
2
INSERM UMR1163, Université Paris Descartes, Paris, France.
3
Department of Experimental Biology, University of Jaén, CU Las Lagunillas, Jaén, Spain.
4
Cardiovascular Development Program, Centro Nacional de Investigaciones Cardiovasculares, CNIC, Madrid, Spain.
5
University of East Anglia, Norwich, United Kingdom.
6
John Innes Centre, Norwich Research Park, Norwich, United Kingdom.
7
The Francis Crick Institute, London, United Kingdom.
#
Contributed equally

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.

KEYWORDS:

3D shape; computer modelling; developmental biology; heart morphogenesis; left-right patterning; mouse; stem cells

Comment in

PMID:
29179813
PMCID:
PMC5705212
DOI:
10.7554/eLife.28951
[Indexed for MEDLINE]
Free PMC Article

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