INDUCTION OF CHONDROGENESIS - REQUIREMENT FOR SYNERGISTIC INTERACTIONOF BASIC FIBROBLAST GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA

Interactions between the epithelial anlage of the developing mouse inn er ear and its associated periotic mesenchyme control the differentiat ion of the cartilaginous otic capsule. Transforming growth factor-beta (1) (TGF-beta(1)) is a naturally occurring signal peptide that is pres ent in these tissues at times of active differentiation and morphogene sis. Previous studies have shown that TGF-beta(1) alone is not a suffi cient stimulus to initiate chondrogenesis in cultured periotic mesench yme. In this study, we provide evidence that basic fibroblast growth f actor (bFGF) can elicit a specific but limited chondrogenic response i n cultured periotic mesenchymal cells. We also demonstrate that simult aneous addition of bFGF and TGF-beta(1) to cultured periotic mesenchym e results in a full chondrogenic response comparable to that which occ urs when periotic mesenchyme is grown in the presence of its natural i nductor tissue (i.e. otic epithelium). Utilizing antibodies directed a gainst bFGF, we show localization of endogenous bFGF in the otic epith elium in vivo and in mixed epithelial-mesenchymal cultures. Additional ly, we demonstrate the presence of FGF-like activity in medium conditi oned by otic epithelium. Blocking of epithelial elicited chondrogenesi s by a combination of both alpha bFGF and alpha TGF-beta(1) antibodies provides further evidence of the necessity for these growth factors i n the chondrogenic differentiation of periotic mesenchyme in vitro. Ou r results suggest a role for both bFGF and TGF-beta(1) in the regulati on of chondrogenesis during otic capsule formation in situ.