oa Contribution of epicardially derived cells to the leaflets of the murine AV valves

To determine the spatiotemporal contribution of epicardially derived cells (EPDCs) to the leaflets of the developing atrioventricular (AV) valves in the murine heart we have used a mWt1/IRES/GFP-Cre mouse and traced the fate of EPDCs from embryonic day (ED)10 until birth. Migration of EPDCs into the mesenchyme of the AV cushions starts around ED12. As development progresses, the number of EPDCs increases significantly, specifically in the leaflets that derive from the lateral atrioventricular cushions, i.e. the mural leaflet of the left AV valve and the lateral leaflet of the right AV valve. In these developing leaflets the EPDCs eventually largely replace the endocardially-derived cells. Importantly, the contribution of EPDCs to the leaflets derived from the major AV cushions is very limited. The differential contribution of EPDCs to the respective leaflets of the atrioventricular valves provides a new paradigm in valve development and could lead to new insights into the pathogenesis of abnormalities that preferentially affect individual components of this region of the heart. The notion that there is a significant difference in the contribution of epicardially and endocardially derived cells to the individual leaflets of the atrioventricular valves has also important pragmatic consequences for the use of endocardial and epicardial cre-mouse models in heart development.