BMP signaling during bone pattern determination in the developing limb

Yasuhiko Kawakami, Tetsuya Ishikawa, Masakiyo Shimabara, Nobuya Tanda, Motomi Enomoto-lwamoto, Masahiro Iwamoto, Takashi Kuwana, Ayako Ueki, Sumlhare Noji, Tsutomu Nohno

Research output: Contribution to journalArticlepeer-review

165 Scopus citations


To examine the role of BMP signaling during limb pattern formation, we isolated chicken cDNAs encoding type I (BRK-1 and BRK-2) and type II (BRK-3) receptors for bone morphogenetic proteins. BRK-2 and BRK-3, which constitute dual-affinity signaling receptor complexes for BMPs, are co-expressed in condensing precartilaginous cells, while BRK-1 is weakly expressed in the limb mesenchyme. BRK-3 is also expressed in the apical ectodermal ridge and interdigital limb mesenchyme. BRK-2 is intensely expressed in the posterior-distal region of the limb bud. During digit duplication by implanting Sonic hedgehog-producing cells, BRK-2 expression is induced anteriorly in the new digit forming region as observed for BMP-2 and BMP-7 expression in the limb bud. Dominant-negative effects on BMP signaling were obtained by overexpressing kinase domain-deficient forms of the receptors. Chondrogenesis of limb mesenchymal cells is markedly inhibited by dominant-negative BRK-2 and BRK-3, but not by BRK-1. Although the bone pattern was not disturbed by expressing individual dominant-negative BRK independently, preferential distal and posterior limb truncations resulted from co-expressing the dominant-negative forms of BRK-2 and BRK-3 in the whole limb bud, thus providing evidence that BMPs are essential morphogenetic signals for limb bone patterning.

Original languageEnglish (US)
Pages (from-to)3557-3566
Number of pages10
Issue number11
StatePublished - 1996


  • BMP
  • BMP receptor
  • Chick
  • Chondrogenesis
  • Limb
  • Pattern formation


Dive into the research topics of 'BMP signaling during bone pattern determination in the developing limb'. Together they form a unique fingerprint.

Cite this