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> Stages de M2 > Liste des stages proposés pour l’année 2017-2018 > Identification of novel left-right markers during heart looping

Identification of novel left-right markers during heart looping

proposé par Sigolène Meilhac, Imagine-Institut Pasteur group of Heart Morphogenesis Institut Imagine, UMR-1163 INSERM 24 boulevard du Montparnasse 75015 PARIS

Projet de stage : The alignment of cardiac chambers is key for the correct plumbing of the blood, so that carbonated blood in the right heart is separated from oxygenated blood in the left heart. Initially, in the heart primordium, the right ventricle is positioned cranially to the left ventricle. It is during the process referred to as cardiac looping, that the right ventricle acquires its position to the right of the left ventricle. Cardiac looping corresponds to a rapid change in heart geometry, from a straight tube to a helical tube. Heart looping is the first morphological sign of left-right asymmetry during embryonic development. It has been shown to depend on left-right patterning, initiated one day earlier in the left-right organiser of the embryo. In humans, mutations disrupting the left-right organiser are associated with heterotaxy, including complex cardiac malformations. However, how information from the left-right organiser is transposed into cardiac cells remains poorly understood. The laboratory has recently developed a computer model of heart looping, as well as tools to stage heart looping and quantify in 3D the associated morphological changes. The master project aims at establishing experimental conditions to identify markers of left-right asymmetry during heart looping. A recent transcriptomic approach, tomo-seq, which determines expression profiles with a spatial resolution, will be implemented in collaboration. Alternatively, cell surface markers will be validated to determine a cell sorting strategy for a single cell transcriptomic approach. The project, which can be extended for a PhD, is expected to provide novel insight into how heart morphogenesis is imprinted by left-right patterning. Our work in the mouse is relevant to congenital heart defects in humans, which is explored with our collaborators of the Hospital Necker-Enfants Malades.

Techniques mises en œuvre par le stagiaire : Transcriptomics, mouse genetics, High Resolution Episcopic Microscopy, quantitative image analysis, bioinformatics and biostatistics

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