Fig. 8. BMP signaling delays terminal hypertrophic differentiation independent of the Ihh/PTHrP system. Forelimbs of E14.5 mouse embryos were cultured for 2 days in control medium (A,B) or in medium supplemented with cyclopamine (C,D), Noggin and cyclopamine (E,F), Noggin (G,H), Noggin and PTHrP (I,J) or PTHrP (K,L). Serial sections were hybridized with riboprobes for ColX (A,C,E,G,I,K) or Osp (B,D,F,H,J,L). (A-D) Cyclopamine treated limbs show increased expression of ColX (C) but normal expression of the marker for terminally differentiated cells, Osp (D) compared with untreated limbs (A,B). (E-H) Noggin treatment results in reduced expression of ColX (G) and significantly increased expression of Osp (H), similar to co-treatment with Noggin and cyclopamine (E,F). (I-L) Limbs treated with PTHrP show reduced expression of ColX (K), which is further reduced in explants double treated with Noggin and PTHrP (I). The low expression of Osp after PTHrP treatment (L) is increased in limbs co-treated with Noggin and PTHrP (J). In all panels, ulna is upwards and radius is downwards. cycl, cyclopamine; Nog, Noggin.