Understanding the cellular bases of mammalian heart morphogenesis is essential to unravel the link between genotype and phenotype, as a complement to knockout experiments. I discovered during my PhD in France two characteristics of the myocardium in the mo use embryo. It is composed of two lineages, which contribute differently to the cardiac tube, and its growth is oriented specifically in the different cardiac chambers. I would like to pursue these lines of research, having gained, during my post-doc in the UK, tools to study cell behaviour in the mouse embryo. I wish to understand when and how myocardial lineages are segregated in the early mouse embryo.
The second lineage will be monitored, by creating a mouse line targeted to the Isl1 locus. With a microinjection approach in collaboration with K. Lawson (Edinburgh), I shall map the myocardial lineages in the E6.5 epiblast onwards. In the longer term, microinjection of molecular perturbations is envisaged, to decipher the mechanism, which specifies lineage identity. Alternatively, to test the role of oriented cell growth in cardiac chamber expansion, I shall use a computer modelling approach in an interdisciplinary collaboration with M. Kerszberg (Paris). Immunofluorescence experiments and explant cultures will provide parameters for the model.
Electroporation experiments should help to characterise the regulation of oriented growth. The project fits well with the strategic objectives of the European Community. It will ensure the reintegration of a young woman researcher in her country, on the way towards independence, as well as a transfer of competencies between two leading European laboratories in the UK and France. With an original contribution to the characterisation of the in vivo behaviour of mammalian embryonic stem cells, when they take first decisions to form the heart, the project is relevant to the understanding of congenital heart disease and to the development of cell therapies for cardiac repair.
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