We specifically studied apoptosis at the level of the aortic sac, where the AP-septum forms between the origins of 4th and 6th PAAs. Already at E10.5, we could see intense apoptosis among the postmigratory NCCs in the mesenchyme surrounding the aortic sac at the site where the prospective AP septum forms, i.e., this cell death precedes the AP septal defect seen in mutants. Although some NC-derived cells appeared to be differentiating to smooth muscle cells in the OFT (Fig. 6), we could never detect the AP septum forming in Alk5/Wnt1-Cre mutants between E10.5 and E11.5. These findings suggest that the pool of cells forming the AP septum is severely affected by the cell death. Moreover, it is likely that these cells forming the AP-septum die the before majority of them can differentiate to smooth muscle cells.