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 journalArticle

157 Citations (Scopus)

Abstract

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
Pages (from-to)3557-3566
Number of pages10
JournalDevelopment
Volume122
Issue number11
Publication statusPublished - 1996
Externally publishedYes

Fingerprint

Extremities
Limb Buds
Bone and Bones
Bone Morphogenetic Protein Receptors
Mesoderm
Bone Morphogenetic Protein 3
Bone Morphogenetic Protein 7
Chondrogenesis
Hedgehogs
Chickens
Phosphotransferases
Complementary DNA

Keywords

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

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Kawakami, Y., Ishikawa, T., Shimabara, M., Tanda, N., Enomoto-lwamoto, M., Iwamoto, M., ... Nohno, T. (1996). BMP signaling during bone pattern determination in the developing limb. Development, 122(11), 3557-3566.

BMP signaling during bone pattern determination in the developing limb. / Kawakami, Yasuhiko; Ishikawa, Tetsuya; Shimabara, Masakiyo; Tanda, Nobuya; Enomoto-lwamoto, Motomi; Iwamoto, Masahiro; Kuwana, Takashi; Ueki, Ayako; Noji, Sumlhare; Nohno, Tsutomu.

In: Development, Vol. 122, No. 11, 1996, p. 3557-3566.

Research output: Contribution to journalArticle

Kawakami, Y, Ishikawa, T, Shimabara, M, Tanda, N, Enomoto-lwamoto, M, Iwamoto, M, Kuwana, T, Ueki, A, Noji, S & Nohno, T 1996, 'BMP signaling during bone pattern determination in the developing limb', Development, vol. 122, no. 11, pp. 3557-3566.
Kawakami Y, Ishikawa T, Shimabara M, Tanda N, Enomoto-lwamoto M, Iwamoto M et al. BMP signaling during bone pattern determination in the developing limb. Development. 1996;122(11):3557-3566.
Kawakami, Yasuhiko ; Ishikawa, Tetsuya ; Shimabara, Masakiyo ; Tanda, Nobuya ; Enomoto-lwamoto, Motomi ; Iwamoto, Masahiro ; Kuwana, Takashi ; Ueki, Ayako ; Noji, Sumlhare ; Nohno, Tsutomu. / BMP signaling during bone pattern determination in the developing limb. In: Development. 1996 ; Vol. 122, No. 11. pp. 3557-3566.
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