Ventricular-subventricular zone fractones are speckled basement membranes that function as a neural stem cell niche.
Ventricular-subventricular zone fractones are speckled basement membranes that function as a neural stem cell niche.
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DOI：
10.1091/mbc.e18-05-0286
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Sekiguchi K
中科院分区：
文献类型：
--
作者：
Sato Y;Kiyozumi D;Futaki S;Nakano I;Shimono C;Kaneko N;Ikawa M;Okabe M;Sawamoto K;Sekiguchi K
神经干细胞（NSCs）保留在成年脑室-脑室下区（V-SVZ），这是一种具有独特细胞结构的特殊神经源性小生境。目前尚不清楚神经干细胞是否或如何利用基底膜（BM）在这个利基。在这里，我们研究的分子组成和功能的BM在成年小鼠V-SVZ。整体安装V-SVZ免疫染色显示，fractones，这是指状过程的血管外BM，斑点BM不连接到脉管系统，并从血管BM在其分子组成不同。胶质细胞酸性蛋白（GFAP）阳性星形胶质细胞和神经干细胞产生并粘附于斑点状BM。此外，Gfap-Cre介导的Lamc 1flox（E1605 Q）敲入小鼠，其中层粘连蛋白的整合素结合活性在GFAP阳性细胞中特异性无效，表现出斑点BM的数量和大小减少，体外神经球形成活性降低。我们的研究结果揭示了神经干细胞的fractones/斑点BM的生态位活动，并为层粘连蛋白-整合素相互作用如何在体内调节神经干细胞提供了分子见解。
Neural stem cells (NSCs) are retained in the adult ventricular–subventricular zone (V-SVZ), a specialized neurogenic niche with a unique cellular architecture. It currently remains unclear whether or how NSCs utilize basement membranes (BMs) in this niche. Here, we examine the molecular compositions and functions of BMs in the adult mouse V-SVZ. Whole-mount V-SVZ immunostaining revealed that fractones, which are fingerlike processes of extravascular BMs, are speckled BMs unconnected to the vasculature, and differ in their molecular composition from vascular BMs. Glial fibrillary acidic protein (GFAP)-positive astrocytes and NSCs produce and adhere to speckled BMs. Furthermore, Gfap-Cre-mediated Lamc1flox(E1605Q) knockin mice, in which integrin-binding activities of laminins are specifically nullified in GFAP-positive cells, exhibit a decreased number and size of speckled BMs and reduced in vitro neurosphere-forming activity. Our results reveal niche activities of fractones/speckled BMs for NSCs and provide molecular insights into how laminin–integrin interactions regulate NSCs in vivo.