Notch是大腦皮層發(fā)育過程中決定神經(jīng)干細(xì)胞/前體細(xì)胞命運(yùn)的重要分子開關(guān)。細(xì)胞生化實(shí)驗(yàn)顯示解整聯(lián)蛋白金屬蛋白酶10很可能是Notch信號通路激活的限速酶,。在小鼠大腦胚胎發(fā)育早期敲除解整聯(lián)蛋白金屬蛋白酶10可以造成神經(jīng)干細(xì)胞數(shù)量的下降,，然而解整聯(lián)蛋白金屬蛋白酶10在大腦皮層胚胎發(fā)育晚期的表達(dá)和作用依然不清。2013年1月第1期《中國神經(jīng)再生研究（英文版）》雜志發(fā)表的一項(xiàng)研究“A Disintegrin and Metalloprotease 10 in neuronal maturation and gliogenesis during cortex development”顯示,，解整聯(lián)蛋白金屬蛋白酶10與NICD在大腦皮層胚胎發(fā)育晚期表達(dá)區(qū)域一致,。有趣的是，解整聯(lián)蛋白金屬蛋白酶10的表達(dá)區(qū)域不僅與成熟神經(jīng)元的分布有部分重疊,，還與膠質(zhì)細(xì)胞分布區(qū)有較好的重疊,。這些結(jié)果表明,，作為Notch信號通路重要的調(diào)控酶，解整聯(lián)蛋白金屬蛋白酶10可能在大腦皮層發(fā)育過程中的神經(jīng)元成熟與神經(jīng)膠質(zhì)細(xì)胞生成中都發(fā)揮一定作用,。解整聯(lián)蛋白金屬蛋白酶10-Notch 信號通路對于大腦皮質(zhì)的形成,、發(fā)育有關(guān)鍵作用。研究為中樞神經(jīng)系統(tǒng)的形成,、神經(jīng)發(fā)生的研究提供了實(shí)驗(yàn)數(shù)據(jù),。（生物谷Bioon.com）
doi:10.3969/j.issn.1673-5374.2013.01.003
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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.
