Our heart is composed of four chambers, two ventricles and two atria arranged in parallel and driving blood from the body to the lungs and through the rest of the body. We have recently contributed to identifying the origin of the cardiac progenitors in the early mouse embryo. We found that the cells comprising the different parts of the heart myocardium have a distinct spatial and temporal origin in the primitive streak (the early embryonic structure that gives rise to mesodermal and endodermal tissues during gastrulation). The ventricular progenitors are the first to leave the streak, followed by progenitors contributing to the atrium and outflow tract.

We are currently investigating if cardiomyocyte cell-type specification and final positioning in the initial heart primordium depend on cells' initial conditions in the primitive streak. In such a model, cells would be predetermined, and their migration path instructed downstream of a genetic cascade established in the primitive streak. Nevertheless, the early embryo is highly regulative. If a cell gets "accidentally" misplaced during migration, it can alter its fate to ensure development continues despite the perturbation. Thus, in addition to being pre-patterned, we further investigate how cells respond to the cellular and signalling environment they encounter during migration to acquire correct cell fates and robustly generate a heart. In the future, it would be important to determine if this principle that cells might be predetermined at much earlier stages than anticipated holds true for other tissues and organs. Addressing this question has important implications for the design of regenerative methods targeting specific populations of cells.