Morphogenesis of outflow tract rotation during cardiac development: the pulmonary push concept

Dev Dyn. 2012 Sep;241(9):1413-22. doi: 10.1002/dvdy.23833. Epub 2012 Jul 30.

Abstract

Background: Understanding of cardiac outflow tract (OFT) remodeling is essential to explain repositioning of the aorta and pulmonary orifice. In wild type embryos (E9.5-14.5), second heart field contribution (SHF) to the OFT was studied using expression patterns of Islet 1, Nkx2.5, MLC-2a, WT-1, and 3D-reconstructions. Abnormal remodeling was studied in VEGF120/120 embryos.

Results: In wild type, Islet 1 and Nkx2.5 positive myocardial precursors formed an asymmetric elongated column almost exclusively at the pulmonary side of the OFT up to the pulmonary orifice. In VEGF120/120 embryos, the Nkx2.5-positive mesenchymal population was disorganized with a short extension along the pulmonary OFT.

Conclusions: We postulate that normally the pulmonary trunk and orifice are pushed in a higher and more frontal position relative to the aortic orifice by asymmetric addition of SHF-myocardium. Deficient or disorganized right ventricular OFT expansion might explain cardiac malformations with abnormal position of the great arteries, such as double outlet right ventricle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning* / genetics
  • Body Patterning* / physiology
  • Computer Simulation
  • Embryo, Mammalian
  • Gestational Age
  • Heart / anatomy & histology
  • Heart / embryology*
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Lung / embryology
  • Lung / metabolism
  • Lung / physiology*
  • Mechanical Phenomena
  • Mice
  • Mice, Transgenic
  • Models, Cardiovascular
  • Morphogenesis* / genetics
  • Morphogenesis* / physiology
  • Rotation
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • Nkx2-5 protein, mouse
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse