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

Dev Cell. 2014 Dec 22;31(6):707-21. doi: 10.1016/j.devcel.2014.11.023.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Calcium-Binding Proteins / metabolism*
  • Cartilage / metabolism
  • Cell Lineage
  • Chondrocytes / cytology
  • Chondrogenesis / physiology*
  • Female
  • Gene Expression Regulation, Developmental*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Jagged-1 Protein
  • Ligands
  • Male
  • Membrane Proteins / metabolism*
  • Mice
  • Muscle Contraction
  • Muscle, Smooth, Vascular / cytology*
  • Myocytes, Smooth Muscle / cytology*
  • Receptors, Notch / metabolism
  • SOX9 Transcription Factor / metabolism*
  • Sequence Analysis, RNA
  • Serrate-Jagged Proteins
  • Signal Transduction
  • Time Factors
  • Transcription Factors / metabolism


  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • Jag1 protein, mouse
  • Jagged-1 Protein
  • Ligands
  • Membrane Proteins
  • Receptors, Notch
  • SOX9 Transcription Factor
  • Serrate-Jagged Proteins
  • Sox9 protein, mouse
  • Transcription Factors