Cadm4 restricts the production of cardiac outflow tract progenitor cells

Cell Rep. 2014 May 22;7(4):951-60. doi: 10.1016/j.celrep.2014.04.013. Epub 2014 May 9.


Heart assembly requires input from two populations of progenitor cells, the first and second heart fields (FHF and SHF), that differentiate at distinct times and create different cardiac components. The cardiac outflow tract (OFT) is built through recruitment of late-differentiating, SHF-derived cardiomyocytes to the arterial pole of the heart. The mechanisms responsible for selection of an appropriate number of OFT cells from the SHF remain unclear. Here, we find that cell adhesion molecule 4 (cadm4) is essential for restricting the size of the zebrafish OFT. Knockdown of cadm4 causes dramatic OFT expansion, and overexpression of cadm4 results in a greatly diminished OFT. Moreover, cadm4 activity limits the production of OFT progenitor cells and the duration of their accumulation at the arterial pole. Together, our data suggest a role for cell adhesion in restraining SHF deployment to the OFT, perturbation of which could cause congenital OFT defects.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cardiac Output / physiology*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion Molecules / physiology*
  • Cell Differentiation / physiology
  • Cell Growth Processes / physiology
  • Gene Knockdown Techniques
  • Myocardium / cytology*
  • Myocardium / metabolism
  • Signal Transduction
  • Stem Cells / cytology*
  • Stem Cells / metabolism
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism
  • Zebrafish Proteins / physiology*


  • Cadm4 protein, zebrafish
  • Cell Adhesion Molecules
  • Zebrafish Proteins

Associated data

  • GEO/GSE55540