Recognition of the neural chemoattractant Netrin-1 by integrins alpha6beta4 and alpha3beta1 regulates epithelial cell adhesion and migration

Dev Cell. 2003 Nov;5(5):695-707. doi: 10.1016/s1534-5807(03)00330-7.


Netrins, axon guidance cues in the CNS, have also been detected in epithelial tissues. In this study, using the embryonic pancreas as a model system, we show that Netrin-1 is expressed in a discrete population of epithelial cells, localizes to basal membranes, and specifically associates with elements of the extracellular matrix. We demonstrate that alpha6beta4 integrin mediates pancreatic epithelial cell adhesion to Netrin-1, whereas recruitment of alpha6beta4 and alpha3beta1 regulate the migration of CK19+/PDX1+ putative pancreatic progenitors on Netrin-1. These results provide evidence for the activation of epithelial cell adhesion and migration by a neural chemoattractant, and identify Netrin-1/integrin interactions as adhesive/guidance cues for epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion / physiology*
  • Cell Line
  • Cell Movement / physiology*
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Extracellular Matrix Proteins / metabolism
  • Humans
  • Integrin alpha3beta1 / metabolism*
  • Integrin alpha6beta4 / metabolism*
  • Nerve Growth Factors / metabolism*
  • Netrin-1
  • Pancreas / cytology
  • Pancreas / embryology
  • Pancreas / metabolism
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Subunits / metabolism
  • Tumor Suppressor Proteins


  • Extracellular Matrix Proteins
  • Integrin alpha3beta1
  • Integrin alpha6beta4
  • NTN1 protein, human
  • Nerve Growth Factors
  • Peptide Fragments
  • Protein Subunits
  • Tumor Suppressor Proteins
  • Netrin-1