Growth differentiation factor 11 signaling controls retinoic acid activity for axial vertebral development

Young Jae Lee, Alexandra McPherron, Susan Choe, Yasuo Sakai, Roshantha A. Chandraratna, Se Jin Lee, S. Paul Oh

Research output: Contribution to journalArticlepeer-review

Abstract

Mice deficient in growth differentiation factor 11 (GDF11) signaling display anterior transformation of axial vertebrae and truncation of caudal vertebrae. However, the in vivo molecular mechanisms by which GDF11 signaling regulates the development of the vertebral column have yet to be determined. We found that Gdf11 and Acvr2b mutants are sensitive to exogenous RA treatment on vertebral specification and caudal vertebral development. We show that diminished expression of Cyp26a1, a retinoic acid inactivating enzyme, and concomitant elevation of retinoic acid activity in the caudal region of Gdf11-/- embryos may account for this phenomenon. Reduced expression or function of Cyp26a1 enhanced anterior transformation of axial vertebrae in wild-type and Acvr2b mutants. Furthermore, a pan retinoic acid receptor antagonist (AGN193109) could lessen the anterior transformation phenotype and rescue the tail truncation phenotype of Gdf11-/- mice. Taken together, these results suggest that GDF11 signaling regulates development of caudal vertebrae and is involved in specification of axial vertebrae in part by maintaining Cyp26a1 expression, which represses retinoic acid activity in the caudal region of embryos during the somitogenesis stage.

Original languageEnglish (US)
Pages (from-to)195-203
Number of pages9
JournalDevelopmental biology
Volume347
Issue number1
DOIs
StatePublished - Nov 1 2010

Keywords

  • ACVR2
  • CYP26A1
  • GDF11
  • RAR inhibitor
  • Retinoic acid
  • Vertebral patterning

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Growth differentiation factor 11 signaling controls retinoic acid activity for axial vertebral development'. Together they form a unique fingerprint.

Cite this