title: Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin.
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.
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: K
authors.initials: K
authors.lastname: Long
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: L
authors.initials: L
authors.lastname: Moss
authors.affiliation: Department of Molecular biology and Genetics, Aarhus University, Gustav Wieds Vej 10 C, 8000 Aarhus C, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Laursen
authors.affiliation: MRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: L
authors.initials: L
authors.lastname: Boulter
authors.affiliation: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
authors.forename: C
authors.initials: C
authors.lastname: Ffrench-Constant
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002540:Cerebral Cortex / Q000196:embryology*; D002642:Chick Embryo; D058575:Decorin / Q000235:genetics* / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D019012:Integrin beta1 / Q000235:genetics* / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D058575:Decorin; D019012:Integrin beta1; C490509:WNT7A protein, Gallus gallus; D051153:Wnt Proteins
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