Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews...
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • Allergy (Apr 2019)
    • Biology of familial cancer predisposition syndromes (Feb 2019)
    • Mitochondrial dysfunction in disease (Aug 2018)
    • Lipid mediators of disease (Jul 2018)
    • Cellular senescence in human disease (Apr 2018)
    • View all review series...
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Scientific Show Stoppers
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Current issue
  • Past issues
  • By specialty
  • Subscribe
  • Alerts
  • Advertise
  • Contact
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • Brief Reports
  • Technical Advances
  • Commentaries
  • Editorials
  • Hindsight
  • Review series
  • Reviews
  • The Attending Physician
  • First Author Perspectives
  • Scientific Show Stoppers
  • Top read articles
  • Concise Communication
Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves
Rajan Jain, … , Lijun Yuan, Jonathan A. Epstein
Rajan Jain, … , Lijun Yuan, Jonathan A. Epstein
Published January 4, 2011; First published December 13, 2010
Citation Information: J Clin Invest. 2011;121(1):422-430. https://doi.org/10.1172/JCI44244.
View: Text | PDF
Categories: Research Article Development

Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves

  • Text
  • PDF
Abstract

Congenital anomalies of the aortic valve are common and are associated with progressive valvular insufficiency and/or stenosis. In addition, aneurysm, coarctation, and dissection of the ascending aorta and aortic arch are often associated conditions that complicate patient management and increase morbidity and mortality. These associated aortopathies are commonly attributed to turbulent hemodynamic flow through the malformed valve leading to focal defects in the vessel wall. However, numerous surgical and pathological studies have identified widespread cystic medial necrosis and smooth muscle apoptosis throughout the aortic arch in affected patients. Here, we provide experimental evidence for an alternative model to explain the association of aortic vessel and valvular disease. Using mice with primary and secondary cardiac neural crest deficiencies, we have shown that neural crest contribution to the outflow endocardial cushions (the precursors of the semilunar valves) is required for late gestation valvular remodeling, mesenchymal apoptosis, and proper valve architecture. Neural crest was also shown to contribute to the smooth muscle layer of the wall of the ascending aorta and aortic arch. Hence, defects of cardiac neural crest can result in functionally abnormal semilunar valves and concomitant aortic arch artery abnormalities.

Authors

Rajan Jain, Kurt A. Engleka, Stacey L. Rentschler, Lauren J. Manderfield, Li Li, Lijun Yuan, Jonathan A. Epstein

×

Figure 1

Loss of Pax3 results in abnormal semilunar valve leaflets.

Options: View larger image (or click on image) Download as PowerPoint
Loss of Pax3 results in abnormal semilunar valve leaflets.
3D reconstruc...
3D reconstruction of OPT images of E16.5 Pax3Cre/+ control embryos demonstrates a trileaflet aortic (A) and pulmonic (B) valve, each with 3 commissures, while Pax3Cre/Cre mutant embryos demonstrate abnormal semilunar valve leaflets. The mutant depicted in C displays a truncal valve with 4 leaflets. Insets in A–C represent identical images with each leaflet pseudocolored. Cross-sectional H&E images through the pulmonic valve leaflets of E16.5 Pax3+/+ and Pax3Cre/+ embryos (D and E) and a Pax3Cre/Cre littermate (F) show thickened leaflets in the mutant. Cross-sectional H&E images through the aortic valve leaflets of E16.5 Pax3+/+ and Pax3Cre/+ embryos (G and H) and a Pax3Cre/Cre littermate (I) show thickened, unequally sized leaflets in the mutant. Examples of a truncal valve (F) and double-outlet right ventricle (I) are shown. Modified Movat’s Pentachrome staining reveals extracellular matrix deposition (blue) in E16.5 control semilunar valve leaflets (J and K) and Pax3Cre/Cre embryos (L), which show an increase in extracellular matrix compared with control leaflets. Higher magnification images of J–L are shown as M–O. AV, aortic valve; PV, pulmonic valve; TrV, truncal valve. Brightness and contrast of OPT images were adjusted using OsiriX software. Scale bars: 100 μm.
Follow JCI:
Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts