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Genes and Development
Vol. 11, No. 17,
pp. 2191-2203,
September 1, 1997
1 Cell Biology and
2 Molecular Biology Programs,
3 Howard Hughes Medical Institute, Memorial Sloan-Kettering
Cancer Center, New York, New York 10021 USA
The bone morphogenetic proteins (BMPs), TGF
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 signaling systems, different type I
receptor isoforms are dedicated to specific functions during
embryogenesis.
[Key Words: Bone morphogenetic proteins; BMP receptor; cartilage differentiation; cell death; chondrogenesis; limb development]
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