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

• Published in: Nature communications Vol. 7; no. 1; p. 10354
• Main Authors: Long, K., Moss, L., Laursen, L., Boulter, L., ffrench-Constant, C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-02-2016; Nature Publishing Group; Nature Portfolio
• Subjects: 101/1; 14; 14/19; 38/61; 42/44; 631/136/368; 631/378/2571/2579; 631/80/79/1236; 631/80/86; 82/51; 96/109; 96/31; 96/35; 96/95; Animal models; Animals; Avian Proteins - genetics; Avian Proteins - metabolism; Cell Differentiation - genetics; Cell proliferation; Cell Proliferation - genetics; Central nervous system; Cerebral cortex; Cerebral Cortex - embryology; Chick Embryo; Decorin; Decorin - genetics; Decorin - metabolism; Differentiation; Extracellular matrix; Extracellular Matrix - metabolism; Gene expression; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Humanities and Social Sciences; Integrin beta1 - genetics; Integrin beta1 - metabolism; Integrins; Mesencephalon; multidisciplinary; Neural stem cells; Neural Stem Cells - metabolism; Neuroepithelial Cells - metabolism; Neurogenesis; Neurogenesis - genetics; Proteins; Receptors; Science; Science (multidisciplinary); Signal transduction; Signal Transduction - genetics; Signaling; Stem cell transplantation; Stem cells; Stem Cells - metabolism; Ventricle; Wnt Proteins - genetics; Wnt Proteins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10354

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.
The extracellular matrix is suggested to play a role in neurogenesis, but it is unclear what role integrin signalling may play in the developing neuroepithelium. Here, in chick, Long
et al
. show that expression of constitutively active integrin beta-1 enhances neurogenesis via a novel Wnt7 and decorin pathway.