Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms10354
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Funding
- Medical Research Council [MR/K015710/1] Funding Source: Medline
- Biotechnology and Biological Sciences Research Council [BB/L00402X/1, BBS/E/D/20310000] Funding Source: researchfish
- Medical Research Council [MR/K015710/1] Funding Source: researchfish
- Wellcome Trust [104783/Z/14/Z] Funding Source: researchfish
- Wellcome Trust [104783/Z/14/Z] Funding Source: Wellcome Trust
- BBSRC [BBS/E/D/20310000, BB/L00402X/1] Funding Source: UKRI
- MRC [MR/K015710/1] Funding Source: UKRI
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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(star)beta 1) in the embryonic chick mesencephalon, enhances neurogenesis and increases the number of mitotic cells dividing away from the ventricular surface, analogous to subapical progenitors in mouse. Only non-integrin-expressing neighbouring cells (lacking CA(star)beta 1) contributed to the increased neurogenesis. Transcriptome analysis reveals upregulation of Wnt7a within the CA(star)beta 1 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.
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