Notch是大脑皮层发育过程中决定神经干细胞/前体细胞命运的重要分子开关。细胞生化实验显示解整联蛋白金属蛋白酶10很可能是Notch信号通路激活的限速酶。在小鼠大脑胚胎发育早期敲除解整联蛋白金属蛋白酶10可以造成神经干细胞数量的下降,然而解整联蛋白金属蛋白酶10在大脑皮层胚胎发育晚期的表达和作用依然不清。2013年1月第1期《中国神经再生研究(英文版)》杂志发表的一项研究“A Disintegrin and Metalloprotease 10 in neuronal maturation and gliogenesis during cortex development”显示,解整联蛋白金属蛋白酶10与NICD在大脑皮层胚胎发育晚期表达区域一致。有趣的是,解整联蛋白金属蛋白酶10的表达区域不仅与成熟神经元的分布有部分重叠,还与胶质细胞分布区有较好的重叠。这些结果表明,作为Notch信号通路重要的调控酶,解整联蛋白金属蛋白酶10可能在大脑皮层发育过程中的神经元成熟与神经胶质细胞生成中都发挥一定作用。解整联蛋白金属蛋白酶10-Notch 信号通路对于大脑皮质的形成、发育有关键作用。研究为中枢神经系统的形成、神经发生的研究提供了实验数据。(生物谷Bioon.com)
doi:10.3969/j.issn.1673-5374.2013.01.003
PMC:
PMID:
A Disintegrin and Metalloprotease 10 in neuronal maturation and gliogenesis during cortex development
Zhixing Ma, Qingyu Li, Zhengyu Zhang, Yufang Zheng
The multiple-layer structure of the cerebral cortex is important for its functions. Such a structure is generated based on the proliferation and differentiation of neural stem/progenitor cells. Notch functions as a molecular switch for neural stem/progenitor cell fate during cortex development but the mechanism remains unclear. Biochemical and cellular studies showed that Notch receptor activation induces several proteases to release the Notch intracellular domain (NICD). A Disintegrin and Metalloprotease 10 (ADAM10) might be a physiological rate-limiting S2 enzyme for Notch activation. Nestin-driven conditional ADAM10 knockout in mouse cortex showed that ADAM10 is critical for maintenance of the neural stem cell population during early embryonic cortex development. However, the expression pattern and function of ADAM10 during later cerebral cortex development remains poorly understood. We performed in situ hybridization for ADAM10 mRNA and immunofluorescent analysis to determine the expression of ADAM10 and NICD in mouse cortex from embryonic day 9 (E14.5) to postnatal day 1 (P1). ADAM10 and NICD were highly co-localized in the cortex of E16.5 to P1 mice. Comparisons of expression patterns of ADAM10 with Nestin (neural stem cell marker), Tuj1 (mature neuron marker), and S100β (glia marker) showed that ADAM10 expression highly matched that of S100β and partially matched that of Tuj1 at later embryonic to early postnatal cortex developmental stages. Such expression patterns indicated that ADAM10-Notch signaling might have a critical function in neuronal maturation and gliogenesis during cortex development.