Fig. 7. BMP and Ihh signaling regulate chondrocyte proliferation in parallel pathways. Forelimbs of E14.5 mouse embryos were cultured for 2 days in control medium (A,D) or in medium supplemented with Noggin (B,C), BMP2 (E), BMP2 and cyclopamine (F) or cyclopamine (G). Limbs in A,B,E-G were derived from wild-type mice, and limbs in C,D from ColII/Ihh embryos. Proliferating cells were labeled with BrdU and detected by antibody staining. (A,B) Noggin treatment results in a block of chondrocyte proliferation (B) compared with untreated limbs (A). Explants from ColII/Ihh embryos show a high level of chondrocyte proliferation (D), which is blocked after Noggin treatment (C). (E-G) BMP2 treatment results in an increased zone of proliferating cells (E) but cannot overcome the cyclopamine-induced block of chondrocyte proliferation (G) in explants double treated with BMP2 and cyclopamine (F). In all panels radius is upwards and ulna is downwards. cycl, cyclopamine; Nog, Noggin.