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Lisbeth Schmidt Laursen

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

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DOI

  • K. Long, Edinburgh University
  • ,
  • L. Moss, Edinburgh University
  • ,
  • Lisbeth Schmidt Laursen
  • L. Boulter, Institute for Genetics and Molecular Medicine
  • ,
  • C. Ffrench-Constant, Edinburgh University

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.

Original languageEnglish
Article number10354
JournalNature Communications
Volume7
ISSN2041-1723
DOIs
Publication statusPublished - 3 Feb 2016

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