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

Long, K., Moss, L., Laursen, L., Boulter, L. and Ffrench-Constant, C. ORCID: (2016) Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin. Nature Communications, 7. ISSN 2041-1723

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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.

Item Type: Article
Additional Information: Funding Information: We thank the National Avian Research Facility, ARK Genomics and the FACS facility for their technical support, especially Kim Bernard, Alison Downing, Fiona Rossi and William Ramsay. Also thanks to Rachel Verdon from the CALM imaging facility. We also thank Veronica Miron for helpful discussion and advice.
Uncontrolled Keywords: chemistry(all),biochemistry, genetics and molecular biology(all),physics and astronomy(all) ,/dk/atira/pure/subjectarea/asjc/1600
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 15 Jul 2022 22:30
Last Modified: 23 Oct 2022 03:56
DOI: 10.1038/ncomms10354

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