The heart functions as a double pump driving the double blood circulation. Failure to partition the heart corresponds to severe structural congenital heart defects. In the embryo, the heart forms as a single tubular primordium, raising the question of how the double blood flow is established during development. We are interested in the mechanisms which remodel the heart tube to align cardiac chambers and great vessels. Using a quantitative approach in the mouse model, we have revisited the process of heart looping and uncovered a maintenance mechanism. We have characterized genetic factors regulating the ingression of precursor cells into the heart tube and identified mechanical constraints, which altogether modulate the heart tube shape. Our work provides novel insight into the origin of heterotaxy and criss-cross heart.
Sigolène Meilhac, is a developmental biologist, INSERM research director, deputy director of the Department of Developmental and Stem Cell Biology of the Institut Pasteur. Trained at the Ecole Normale Supérieure, she acquired expertise in mouse development during her PhD with M. Buckingham (Institut Pasteur) and post-doctoral work at the Gurdon Institute of Cambridge (UK), including seminal publications on myocardial cell lineages. Her team at the Institut Imagine and Institut Pasteur (Paris) now addresses the mechanisms shaping the embryonic heart tube and the embryological origin of structural congenital heart defects with an interdisciplinary approach. The combination of advanced quantitative 3D imaging of shape changes and gene expression with computer simulations and transcriptomic analyses provides novel insight into the formation of the heart. Recent work uncovering mechanisms of heart looping has provided a novel conceptual framework and analytic tools of asymmetric morphogenesis, relevant to the heterotaxy syndrome. Sigolène Meilhac was recipient of the Pasteur Vallery-Radot price in 2018.