Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis

Masahiro Iwamoto, Yoshihiro Tamamura, Eiki Koyama, Toshihisa Komori, Nobuo Takeshita, Julie A. Williams, Takashi Nakamura, Motomi Enomoto-Iwamoto, Maurizio Pacifici

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)

Abstract

Articular cartilage and synovial joints are critical for skeletal function, but the mechanisms regulating their development are largely unknown. In previous studies we found that the ets transcription factor ERG and its alternatively-spliced variant C-1-1 have roles in joint formation in chick. Here, we extended our studies to mouse. We found that ERG is also expressed in developing mouse limb joints. To test regulation of ERG expression, beads coated with the joint master regulator protein GDF-5 were implanted close to incipient joints in mouse limb explants; this led to rapid and strong ectopic ERG expression. We cloned and characterized several mammalian ERG variants and expressed a human C-1-1 counterpart (hERG3Δ81) throughout the cartilaginous skeleton of transgenic mice, using Col2a1 gene promoter/enhancer sequences. The skeletal phenotype was severe and neonatal lethal, and the transgenic mice were smaller than wild type littermates and their skeletons were largely cartilaginous. Limb long bone anlagen were entirely composed of chondrocytes actively expressing collagen IX and aggrecan as well as articular markers such as tenascin-C. Typical growth plates were absent and there was very low expression of maturation and hypertrophy markers, including Indian hedgehog, collagen X and MMP-13. The results suggest that ERG is part of molecular mechanisms leading chondrocytes into a permanent developmental path and become joint forming cells, and may do so by acting downstream of GDF-5.

Original languageEnglish
Pages (from-to)40-51
Number of pages12
JournalDevelopmental Biology
Volume305
Issue number1
DOIs
Publication statusPublished - 2007 May 1
Externally publishedYes

Keywords

  • Articular chondrocytes
  • ERG transcription factor
  • Extracellular matrix
  • GDF-5
  • Limb and spine skeletogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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