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

Journal Article (Journal Article)

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 to fully 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.

Full Text

Duke Authors

Cited Authors

  • Briot, A; Jaroszewicz, A; Warren, CM; Lu, J; Touma, M; Rudat, C; Hofmann, JJ; Airik, R; Weinmaster, G; Lyons, K; Wang, Y; Kispert, A; Pellegrini, M; Iruela-Arispe, ML

Published Date

  • December 22, 2014

Published In

Volume / Issue

  • 31 / 6

Start / End Page

  • 707 - 721

PubMed ID

  • 25535917

Pubmed Central ID

  • PMC4311887

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2014.11.023


  • eng

Conference Location

  • United States