Distinct roles of type I bone morphogenetic protein receptors in the formation and differentiation of cartilage

Hongyan Zou, Rotraud Wieser, Joan Massagué, Lee Niswander

Research output: Contribution to journalArticlepeer-review

466 Scopus citations

Abstract

The bone morphogenetic proteins (BMPs), TGFβ 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 TGFβ signaling systems, different type I receptor isoforms are dedicated to specific functions during embryogenesis.

Original languageEnglish
Pages (from-to)2191-2203
Number of pages13
JournalGenes and Development
Volume11
Issue number17
DOIs
StatePublished - 1 Sep 1997
Externally publishedYes

Keywords

  • BMP receptor
  • Bone morphogenetic proteins
  • Cartilage differentiation
  • Cell death
  • Chondrogenesis
  • Limb development

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