影响大脑皮质神经细胞生成的信号通路.docxVIP

中国神经再生研究(英文版)??2013,?Vol. 8??Issue (1): 24-30????DOI: 10.3969/j.issn.1673-5374.2013.01.003Basic Research影响大脑皮质神经细胞生成的信号通路A Disintegrin and Metalloprotease 10 in neuronal maturation and gliogenesis during cortex development全文:?PDF?(345 KB) ??摘要?Notch是大脑皮质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，而整联蛋白金属蛋白酶10很可能是Notch限速步骤的S2酶。在小鼠大脑皮质早期发育阶段敲除整联蛋白金属蛋白酶10可以造成神经干细胞数量的下降，然而整联蛋白金属蛋白酶10在大脑皮质发育晚期的表达和作用目前依然不清楚。我们研究的目的是鉴定整联蛋白金属蛋白酶10和Notch胞内段在小鼠大脑胚胎发育晚期是否有时空上表达的一致性。我们用原位杂交和免疫荧光组化的方法鉴定了整联蛋白金属蛋白酶10及Notch胞内段在胚胎晚期到出生后P1天内的小鼠大脑皮质中的表达；并将整联蛋白金属蛋白酶10的表达模式与多种标记物的免疫荧光组化结果进行对比，包括标记神经干细胞的Nestin，标记成熟神经元的Tuj1标记，标记胶质细胞的S100beta。结果显示整联蛋白金属蛋白酶10在孕15.5d到生后1d的皮质板和脑室下层区域有表达，并与Notch胞内段有很好的共标区域。整联蛋白金属蛋白酶10的表达区域不仅与Tuj1有部分重叠，还与S100beta标记的区间有较好的重叠。这些结果表明整联蛋白金属蛋白酶10-Notch信号通路可能在大脑皮质发育过程中的神经元成熟与胶质细胞生成中发挥一定作用。关键词：?神经再生；?神经发生；?整联蛋白金属蛋白酶；?Notch胞内段；?大脑皮质；?神经发育；?神经元成熟；?胶质细胞；?基金资助文章；?图片文章； ??Abstract: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