Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin

Nat Commun. 2016 Feb 3:7:10354. doi: 10.1038/ncomms10354.

Abstract

Development of the cerebral cortex requires regulation of proliferation and differentiation of neural stem cells and a diverse range of progenitors. Recent work suggests a role for extracellular matrix (ECM) and the major family of ECM receptors, the integrins. Here we show that enhancing integrin beta-1 signalling, by expressing a constitutively active integrin beta-1 (CA*β1) in the embryonic chick mesencephalon, enhances neurogenesis and increases the number of mitotic cells dividing away from the ventricular surface, analogous to sub-apical progenitors in mouse. Only non-integrin-expressing neighbouring cells (lacking CA*β1) contributed to the increased neurogenesis. Transcriptome analysis reveals upregulation of Wnt7a within the CA*β1 cells and upregulation of the ECM protein Decorin in the neighbouring non-expressing cells. Experiments using inhibitors in explant models and genetic knock-downs in vivo reveal an integrin-Wnt7a-Decorin pathway that promotes proliferation and differentiation of neuroepithelial cells, and identify Decorin as a novel neurogenic factor in the central nervous system.

MeSH terms

  • Animals
  • Avian Proteins / genetics*
  • Avian Proteins / metabolism
  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics*
  • Cerebral Cortex / embryology*
  • Chick Embryo
  • Decorin / genetics*
  • Decorin / metabolism
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation, Developmental*
  • Gene Knockdown Techniques
  • Integrin beta1 / genetics*
  • Integrin beta1 / metabolism
  • Neural Stem Cells / metabolism
  • Neuroepithelial Cells / metabolism*
  • Neurogenesis / genetics*
  • Signal Transduction / genetics
  • Stem Cells / metabolism*
  • Wnt Proteins / genetics*
  • Wnt Proteins / metabolism

Substances

  • Avian Proteins
  • Decorin
  • Integrin beta1
  • WNT7A protein, Gallus gallus
  • Wnt Proteins