As noted above, Bmp2-deficient animals display a variably penetrant 3/4 soft tissue syndactyly phenotype (Figure 2B). In contrast, Bmp4-deficient mice show no evidence of syndactyly (unpublished data). However, one of the striking defects observed in the Bmp2C/C; Bmp4C/C; Prx1::cre mice is that in the newborn animals, the digits of both forelimb (unpublished data) and hindlimb show complete syndactyly (Figure 2D; compare to wild-type, Figure 2C). To determine the origin of this defect, we examined embryonic limbs at E15.5, the stage when interdigital separation is normally taking place (Figure 2E). In Bmp2C/C; Bmp4C/C; Prx1::cre limbs, only the very distal tips of each digit were separated, with the autopod adopting the shape of a notched pallet (Figure 2F). In wild-type development, the individual digits become free from one another through a process of interdigital apoptosis, observable by staining with acridine orange (Figure 2E and 2G, arrow). Interdigital apoptosis is dramatically reduced in the Bmp2C/C; Bmp4C/C; Prx1::cre limbs (Figure 2F and 2H, arrow). (Note that the strong acridine orange staining in Figure 2H is not in the interdigital mesenchyme but rather is in the remnant of the cells of the AER [red asterisk].)