Independent requirements for Hedgehog signaling by both the anterior heart field and neural crest cells for outflow tract development

Development. 2007 Apr;134(8):1593-604. doi: 10.1242/dev.02824. Epub 2007 Mar 7.

Abstract

Cardiac outflow tract (OFT) septation is crucial to the formation of the aortic and pulmonary arteries. Defects in the formation of the OFT can result in serious congenital heart defects. Two cell populations, the anterior heart field (AHF) and cardiac neural crest cells (CNCCs), are crucial for OFT development and septation. In this study, we use a series of tissue-specific genetic manipulations to define the crucial role of the Hedgehog pathway in these two fields of cells during OFT development. These data indicate that endodermally-produced SHH ligand is crucial for several distinct processes, all of which are required for normal OFT septation. First, SHH is required for CNCCs to survive and populate the OFT cushions. Second, SHH mediates signaling to myocardial cells derived from the AHF to complete septation after cushion formation. Finally, endodermal SHH signaling is required in an autocrine manner for the survival of the pharyngeal endoderm, which probably produces a secondary signal required for AHF survival and for OFT lengthening. Disruption of any of these steps can result in a single OFT phenotype.

Publication types

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

MeSH terms

  • Animals
  • Arteries / embryology*
  • Branchial Region / blood supply
  • Branchial Region / embryology*
  • Branchial Region / metabolism
  • Endoderm / metabolism
  • Heart / embryology*
  • Hedgehog Proteins / metabolism
  • Hedgehog Proteins / physiology*
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Morphogenesis
  • Myocardium / cytology
  • Myocardium / metabolism*
  • Myocytes, Cardiac / physiology
  • Neural Crest / embryology*
  • Neural Crest / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism

Substances

  • Hedgehog Proteins
  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • Nkx2-5 protein, mouse
  • Shh protein, mouse
  • Transcription Factors