Distinct roles of type I bone morphogenetic protein receptors in the formation and differentiation of cartilage.
The bone morphogenetic proteins (BMPs), TGF beta superfamily members, play diverse roles in embryogenesis, but how the BMPs exert their action is unclear and how different BMP receptors (BMPRs) contribute to this process is not known. Here we demonstrate that the two type I BMPRs, BMPR-IA and BMPR-IB, regulate distinct processes during chick limb development. BmpR-IB expression in the embryonic limb prefigures the future cartilage primordium, and its activity is necessary for the initial steps of chondrogenesis. During later chondrogenesis, BmpR-IA is specifically expressed in prehypertrophic chondrocytes. BMPR-IA regulates chondrocyte differentiation, serving as a downstream mediator of Indian Hedgehog (IHH) function in both a local signaling loop and a longer-range relay system to PTHrP. BMPR-IB also regulates apoptosis: Expression of activated BMPR-IB results in increased cell death, and we showed 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 embryogenesis.
Zou
H
H
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Wieser
R
R
Massagué
J
J
Niswander
L
L
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002356:Cartilage / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D002454:Cell Differentiation; D002642:Chick Embryo; D005121:Extremities / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D009154:Mutation; D044162:Parathyroid Hormone-Related Protein; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000502:physiology; D012313:RNA / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D015534:Trans-Activators; D016212:Transforming Growth Factor beta / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D017978:Receptors, Growth Factor; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D012313:RNA; D017346:Protein Serine-Threonine Kinases; D052005:Bone Morphogenetic Protein Receptors, Type I