Figure 3.

Lineage tracing of cells in the foetal and neonatal arterial valves. (A) At E12.5, Tie2-Cre labelled endocardial-derived cells, Wnt1-Cre-labelled NCC and Tnnt2-Cre labelled cells derived directly from the SHF, via the outflow wall, are found within the pulmonary valve leaflet primordia. Whilst Tie2-Cre and Wnt1-Cre-labelled cells are most abundant in the left (L) and right (R) leaflets, the Tnnt2-Cre labelled cells are the most abundant in the anterior (A) leaflet derived from the ICVS. Similar observations are made for the aortic valve (not shown). (B) At P2, each of the three lineages of cells are maintained within the leaflets of the aortic valve. As at E12.5, Wnt1-Cre and Tie2-Cre labelled cells are most abundant in the L and R leaflets, whilst Tnnt2-Cre labelled cells are most abundant in the posterior (P) leaflet derived from the ICVS. Similar observations are made for the pulmonary valve (not shown). (C) Cartoon illustrating how arterial valve leaflet formation is intimately linked to outflow tract septation. At E10.5, the forming endocardial cushions (buff coloured) are circumferential within the outflow vessel and the ICVS (grey) can first be seen within the outflow wall (green). By E11.5 the endocardial cushions (buff) have expanded and are coming together to fuse in the midline. Fusion of these cushions separates the outflow tract and gives rise to the L and R valve primordia. The ICVS give rise to the A and P valve primordia. By E13.5 the aortic and pulmonary valve are distinct, and the sinuses are beginning to appear. At E15.5, valve sculpting is almost complete, and the aorta and pulmonary valves are offset. Green = myocardium, yellow = SMC, red = endocardium.