Pitx2 is functionally important in the early stages of vascular smooth muscle cell differentiation

Yueting Shang, Tadashi Yoshida, Brad A. Amendt, James F. Martin, Gary K. Owens

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Mechanisms that control vascular smooth muscle cell (SMC) differentiation are poorly understood. We identify Pitx2 as a previously unknown homeodomain transcription factor that is rapidly induced in an in vitro model of SMC differentiation from multipotent stem cells. Pitx2 induces expression of multiple SMC differentiation marker genes by binding to a TAATC(C/T) cis-element, by interacting with serum response factor, and by increasing histone acetylation levels within the promoters of SMC differentiation marker genes. Suppression of Pitx2 reduces expression of SMC differentiation marker genes in the early stages of SMC differentiation in vitro, whereas Prx1, another homeodomain protein, regulates SMC differentiation marker genes in fully differentiated SMCs. Pitx2, but not Prx1, knockout mouse embryos exhibit impaired induction of SMC differentiation markers in the dorsal aorta and branchial arch arteries. Our results demonstrate that Pitx2 functions to regulate the early stages of SMC differentiation.

Original languageEnglish
Pages (from-to)461-473
Number of pages13
JournalJournal of Cell Biology
Volume181
Issue number3
DOIs
Publication statusPublished - 2008 May 5

ASJC Scopus subject areas

  • Cell Biology

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