Repression of Sox9 by Jag1 is continuously required to suppress the default chondrogenic fate of vascular smooth muscle cells

Anaïs Briot, Artur Jaroszewicz, Carmen M. Warren, Jing Lu, Marlin Touma, Carsten Rudat, Jennifer J. Hofmann, Rannar Airik, Gerry Weinmaster, Karen Lyons, Yibin Wang, Andreas Kispert, Matteo Pellegrini, M. Luisa Iruela-Arispe*

*Corresponding author for this work

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Acquisition and maintenance of vascular smooth muscle fate are essential for the morphogenesis and function of the circulatory system. Loss of contractile properties or changes in the identity of vascular smooth muscle cells (vSMCs) can result in structural alterations associated with aneurysms and vascular wall calcification. Here we report that maturation of sclerotome-derived vSMCs depends on a transcriptional switch between mouse embryonic days 13 and 14.5. At this time, Notch/Jag1-mediated repression of sclerotome transcription factors Pax1, Scx, and Sox9 is necessary tofully enable vSMC maturation. Specifically, Notch signaling in vSMCs antagonizes sclerotome and cartilage transcription factors and promotes upregulation of contractile genes. In the absence of the Notch ligand Jag1, vSMCs acquire a chondrocytic transcriptional repertoire that can lead to ossification. Importantly, our findings suggest that sustained Notch signaling is essential throughout vSMC life to maintain contractile function, prevent vSMC reprogramming, and promote vascular wall integrity.

Original languageEnglish (US)
Pages (from-to)707-721
Number of pages15
JournalDevelopmental Cell
Volume31
Issue number6
DOIs
StatePublished - Dec 22 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Briot, A., Jaroszewicz, A., Warren, C. M., Lu, J., Touma, M., Rudat, C., Hofmann, J. J., Airik, R., Weinmaster, G., Lyons, K., Wang, Y., Kispert, A., Pellegrini, M., & Iruela-Arispe, M. L. (2014). Repression of Sox9 by Jag1 is continuously required to suppress the default chondrogenic fate of vascular smooth muscle cells. Developmental Cell, 31(6), 707-721. https://doi.org/10.1016/j.devcel.2014.11.023