BMP-Smad4 signaling is required for precartilaginous mesenchymal condensation independent of Sox9 in the mouse

Joohyun Lim, Xiaolin Tu, Kyunghee Choi, Haruhiko Akiyama, Yuji Mishina, Fanxin Long

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Bone morphogenetic proteins (BMPs) regulate multiple aspects of skeletal development in vertebrates. Although exogenously applied BMPs can induce chondrogenesis de novo, the role and mechanism of physiologic BMP signaling during precartilaginous mesenchymal condensation is not well understood. By deleting the type I BMP receptors or the transcription factor Smad4 in the limb bud mesenchyme, we find that loss of BMP-Smad signaling abolishes skeletal development due to a failure in mesenchymal condensation. In the absence of Smad4, expression of Sox9, an essential transcription factor for chondrogenesis, initiates normally in the proximal mesenchyme of the limb bud, but fails to maintain its level or expand to the more distal territory at the later stages. However, forced-expression of Sox9 does not restore cartilage formation in the Smad4-deficeint embryo. In vitro micromass cultures show that the Smad4-deficient cells fail to condense in a cell-autonomous manner, even though they express several cell adhesion molecules either normally or even at a higher level. Thus, BMP-Smad signaling critically controls mesenchymal condensation to initiate skeletal development likely through a Sox9-independent mechanism.

Original languageEnglish
Pages (from-to)132-138
Number of pages7
JournalDevelopmental Biology
Volume400
Issue number1
DOIs
StatePublished - Apr 1 2015

Keywords

  • Acvr1
  • Alk2
  • Alk3
  • Alk6
  • BMP
  • Bmpr1a
  • Bmpr1b
  • Cartilage
  • Mesenchymal condensation
  • Mouse
  • Smad4
  • Sox9

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