Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin.
Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin.
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DOI：
10.1038/ncomms10354
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发表时间：
2016-02-03
影响因子：
16.6
通讯作者：
Ffrench-Constant C
中科院分区：
文献类型：
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作者：
Long K;Moss L;Laursen L;Boulter L;Ffrench-Constant C
大脑皮层的发育需要调节神经干细胞和各种各样的祖细胞的增殖和分化。最近的研究表明，细胞外基质（ECM）和ECM受体的主要家族，整合素的作用。本研究表明，通过在胚胎鸡中脑中表达组成型活性整合素β -1 （CA*β1）来增强整合素β -1信号传导，可以促进神经发生，增加从心室表面分裂的有丝分裂细胞的数量，类似于小鼠的亚根尖祖细胞。只有不表达整合素的邻近细胞（缺乏CA*β1）促进了神经发生的增加。转录组分析显示Wnt7a在CA*β1细胞中上调，而在邻近的非表达细胞中上调ECM蛋白Decorin。利用外植体模型和体内基因敲除抑制剂的实验揭示了integrin-Wnt7a-Decorin通路促进神经上皮细胞的增殖和分化，并确定Decorin是中枢神经系统中一种新的神经源性因子。细胞外基质被认为在神经发生中起作用，但整合素信号在发育中的神经上皮中可能起什么作用尚不清楚。在这里，Long等人在小鸡中表明，组成型活性整合素β -1的表达通过一种新的Wnt7和decorin途径增强了神经发生。
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.