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

Autor: Audrey Desgrange, Kenzo Ivanovitch, Timothy J. Mohun, Miguel Torres, Enrico Coen, Jorge N. Domínguez, Sigolène M. Meilhac, Jean-François Le Garrec, Etienne Raphaël, J. Andrew Bangham
Přispěvatelé: Coordination des Cellules et Morphogenèse / Heart Morphogenesis (Imagine - Institut Pasteur U1163), Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Jaén, Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain] (CNIC), Instituto de Salud Carlos III [Madrid] (ISC), University of East Anglia [Norwich] (UEA), John Innes Centre [Norwich], The Francis Crick Institute [London], Agence Nationale de la Recherche 11-JSV2-00601InsermInstitut PasteurInstitut ImagineSpanish Ministry BFU2015-71519-PHuman Frontier Science Pro-gram LT000609/2015EMBOATL1275-2014, ANR-11-JSV2-0006,cardiopol,Polarité des cellules du myocarde au cours de la formation des chambres cardiaques(2011), Institut Pasteur [Paris] (IP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biotechnology and Biological Sciences Research Council (BBSRC), Desgrange, Audrey, Jeunes Chercheuses et Jeunes Chercheurs - Polarité des cellules du myocarde au cours de la formation des chambres cardiaques - - cardiopol2011 - ANR-11-JSV2-0006 - JCJC - VALID, Agence Nationale de la Recherche (Francia), Institut National de la Santé et de la Recherche Médicale (Francia), Institut Pasteur, Ministerio de Economía, Industria y Competitividad (España)
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Heart morphogenesis
Mouse
Organogenesis
Stem cells
Mice
computer modelling
Morphogenesis
symbols.heraldic_charge
Biology (General)
[SDV.BDD]Life Sciences [q-bio]/Development Biology
Microscopy
Heart development
General Neuroscience
Dynamics (mechanics)
Heart shape
Heart
General Medicine
Anatomy
Left-right patterning
symbols
Medicine
Insight
Research Article
QH301-705.5
Science
Embryonic Development
Biology
General Biochemistry
Genetics and Molecular Biology
heart morphogenesis
03 medical and health sciences
Imaging
Three-Dimensional
Developmental biology
None
[SDV.BDD] Life Sciences [q-bio]/Development Biology
Animals
Computer Simulation
Mouse Heart
Process (anatomy)
Body Patterning
General Immunology and Microbiology
left-right patterning
3D shape
Developmental Biology and Stem Cells
030104 developmental biology
Computer modelling
Zdroj: eLife
eLife, eLife Sciences Publication, 2017, 6, ⟨10.7554/eLife.28951⟩
eLife, 2017, 6, ⟨10.7554/eLife.28951⟩
Repisalud
Instituto de Salud Carlos III (ISCIII)
eLife, Vol 6 (2017)
ISSN: 2050-084X
Popis: 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.
eLife digest The heart is an organ that pumps blood throughout the body to supply oxygen and to remove carbon dioxide and waste products. Its left and right side are shaped differently to circulate blood through two pathways: to the lungs and to all other organs. As the heart develops inside the embryo, it transforms from a simple, straight tube into a helix shape similar to the shell of a snail. During this process called looping, the helix coils anti-clockwise, which determines where the left and right side of the heart form. It is thought that over 20% of heart anomalies in children may be caused by abnormal looping. Much of what is known about heart development is based on studies in chicken and fish. However, despite its medical significance, it was not fully understood how the heart of mammals acquires its helix shape. Now, Le Garrec et al. were able to investigate the looping process more closely by creating 3D images and computer simulations of the developing mouse heart. First, Le Garrec et al. studied the cells that build the heart and found that left and right cells contribute differently. For example, the number of cells differed between left and right side. The computer simulations then showed that looping is caused by mechanical constraints, which occur because of the way the heart attaches to the body. These mechanical constraints amplify the differences between left and right cells and cause the heart to acquire an oriented helix shape. The computer model could predict how the heart shape will change depending on the type of mechanical constraint, or if cells will have varying levels of left/right differences. The model could also accurately reproduce the shape changes observed in the mouse embryo and predict the abnormal shape of embryos with a genetic defect. The tools generated in this study will help to understand how anomalies could appear as the heart develops in the embryo, and may in the future also be applied to other organs like the gut. A next step will be to explore how genes control the looping of the heart and contribute to heart anomalies in children.
Databáze: OpenAIRE
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