Activin type IIA and IIB receptors mediate Gdf11 signaling in axial vertebral patterning

S. Paul Oh, Chang Yeol Yeo, Youngjae Lee, Heindrich Schrewe, Malcolm Whitman, En Li

Research output: Contribution to journalArticlepeer-review

158 Scopus citations

Abstract

Vertebral bodies are segmented along the anteroposterior (AP) body axis, and the segmental identity of the vertebrae is determined by the unique expression pattern of multiple Hox genes. Recent studies have demonstrated that a transforming growth factor β (TGF-β) family protein, Gdf11 (growth and differentiation factor 11), and the activin type II receptor, ActRIIB, are involved in controlling the spatiotemporal expression of multiple Hox genes along the AP axis, and that the disruption of each of these genes causes anterior transformation of the vertebrae. Skeletal defects are more severe in Gdf11-null mice than in ActRIIB-null mice, however, leaving it uncertain whether Gdf11 signals via ActRIIB. Here we demonstrate using genetic and biochemical studies that ActRIIB and its subfamily receptor, ActRIIA, cooperatively mediate the Gdf11 signal in patterning the axial vertebrae, and that Gdf11 binds to both ActRIIA and ActRIIB, and induces phosphorylation of Smad2. In addition, we also show that these two receptors can functionally compensate for one another to mediate signaling of another TGF-β ligand, nodal, during left-right patterning and the development of anterior head structure.

Original languageEnglish
Pages (from-to)2749-2754
Number of pages6
JournalGenes and Development
Volume16
Issue number21
DOIs
StatePublished - 1 Nov 2002

Keywords

  • Activin receptor
  • Gdf11
  • Left-right asymmetry
  • Nodal
  • Vertebrae

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