A novel isoform of Vinexin, Vinexin γ, regulates Sox9 gene expression through activation of MAPK cascade in mouse fetal gonad

Makoto Matsuyama, Hirofumi Mizusaki, Akihiko Shimono, Tokuo Mukai, Katsuzumi Okumura, Kuniya Abe, Kiyoshi Shimada, Ken-Ichirou Morohashi

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Recent loss-of-function and gain-of-function studies have revealed that transcription factor Sox9 is required for testis formation by governing Sertoli cell differentiation, and thereafter regulating transcription of Sertoli marker genes. In the present study, we identified a novel isoform of Vinexin, which is expressed in somatic cells but not germ cells of sexually indifferent stages of fetal gonads. After the sex is determined, the expression continues in testicular Sertoli cells. Immunohistochemical analyses with a specific antibody to Vinexin indicated that Vinexin γ is localized in the cytoplasm. Functional studies with C3H10T1/2 cells showed that Vinexin γ acted as a scaffold protein to activate MEK and ERK through interaction with c-Raf and ERK. Ultimately, Sox9 transcription was induced by Vinexin γ. This up-regulation of Sox9 expression disappeared when the cells were treated with a specific MEK inhibitor, U0126. To determine the role of Vinexin γ during gonad formation, the gene was disrupted by targeted mutagenesis. The phenotype displayed by the mice indicated that ERK activation was decreased in the Vinexin γ-/- XY gonads, and Sox9 expression was down-regulated. Thus, Vinexin γ seems to be implicated in regulation of Sox9 gene expression by modulating MAPK cascade in mouse fetal gonads.

Original languageEnglish
Pages (from-to)421-434
Number of pages14
JournalGenes to Cells
Volume10
Issue number5
DOIs
Publication statusPublished - May 1 2005

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Gonads
Protein Isoforms
Gene Expression
Sertoli Cells
Mitogen-Activated Protein Kinase Kinases
Gene Expression Regulation
Germ Cells
Mutagenesis
Genes
Testis
Cell Differentiation
Cytoplasm
Transcription Factors
Up-Regulation
Phenotype
Antibodies
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

Cite this

A novel isoform of Vinexin, Vinexin γ, regulates Sox9 gene expression through activation of MAPK cascade in mouse fetal gonad. / Matsuyama, Makoto; Mizusaki, Hirofumi; Shimono, Akihiko; Mukai, Tokuo; Okumura, Katsuzumi; Abe, Kuniya; Shimada, Kiyoshi; Morohashi, Ken-Ichirou.

In: Genes to Cells, Vol. 10, No. 5, 01.05.2005, p. 421-434.

Research output: Contribution to journalArticle

Matsuyama, Makoto ; Mizusaki, Hirofumi ; Shimono, Akihiko ; Mukai, Tokuo ; Okumura, Katsuzumi ; Abe, Kuniya ; Shimada, Kiyoshi ; Morohashi, Ken-Ichirou. / A novel isoform of Vinexin, Vinexin γ, regulates Sox9 gene expression through activation of MAPK cascade in mouse fetal gonad. In: Genes to Cells. 2005 ; Vol. 10, No. 5. pp. 421-434.
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