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Pitx2 is functionally important in the early stages of vascular smooth muscle cell differentiation
Journal article   Open access   Peer reviewed

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

Yueting Shang, Tadashi Yoshida, Brad A. Amendt, James F. Martin and Gary K. Owens
The Journal of cell biology, Vol.181(3), pp.461-473
05/05/2008
DOI: 10.1083/jcb.200711145
PMCID: PMC2364692
PMID: 18458156
url
https://doi.org/10.1083/jcb.200711145View
Published (Version of record) Open Access

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.
Cell Biology Life Sciences & Biomedicine Science & Technology

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