DISTINCT ROLES OF TYPE-I BONE MORPHOGENETIC PROTEIN RECEPTORS IN THE FORMATION AND DIFFERENTIATION OF CARTILAGE

The bone morphogenetic proteins (BMPs), TGP beta superfamily members, play diverse roles in embryogenesis, but how the BMPs exert their acti on is unclear and how different BMP receptors (BMPRs) contribute to th is process is not known. Here we demonstrate that the two type I BMPRs , BMPR-IA and BMPR-IB, regulate distinct processes during chick limb d evelopment. BmpR-IB expression in the embryonic limb prefigures the fu ture cartilage primordium, and its activity is necessary for the initi al steps of chondrogenesis. During later chondrogenesis, BmpR-IA is sp ecifically expressed in prehypertrophic chondrocytes. BMPR-IA regulate s chondrocyte differentiation, serving as a downstream mediator of Ind ian Hedgehog (IHH) function in both a local signaling loop and a longe r-range relay system to PTHrP. BMPR-IB also regulates apoptosis: Expre ssion of activated BMPR-IB results in increased cell death, and we sho wed previously that dominant-negative BMPR-IB inhibits apoptosis. Our studies indicate that in TGF beta signaling systems, different type I receptor isoforms are dedicated to specific functions during embryogen esis.