β1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance
β1 integrins activate a MAPK signalling pathway in neural stem cells that contributes to their maintenance
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DOI：
10.1242/dev.01199
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发表时间：
2004-07-01
期刊：
影响因子：
4.6
通讯作者：
ffrench-Constant, C
中科院分区：
文献类型：
--
作者：
Campos, LS;Leone, DP;ffrench-Constant, C
干细胞在专门的生态位中发育的新证据凸显了环境因素在其调节中的潜在作用。在这里，我们研究了 β1 整合素/细胞外基质相互作用在神经干细胞中的作用。我们发现胚胎 CNS 的干细胞区域有高水平的 β1 整合素表达，并伴有层粘连蛋白 α2 链的表达。出生后 CNS 中层粘连蛋白 α2 的表达水平降低，但表达高水平 β1 的细胞群仍然存在。使用神经球——源自单个干细胞的聚集培养物，其具有导致定位的三维结构。球体边缘周围干细胞群的分布 - 我们直接证明β1整合素在神经干细胞上高水平表达，可用于神经干细胞的选择。根据神经球形成评估，神经干细胞维持需要 MAPK（而非 PI3K）信号传导，并且使用 cre/lox 技术抑制或基因消除 β1 整合素会降低 MAPK 活性水平。因此，我们得出的结论是，整合素是控制中枢神经系统特定区域神经干细胞行为的信号传导机制的重要组成部分。
The emerging evidence that stem cells develop in specialised niches highlights the potential role of environmental factors in their regulation. Here we examine the role of beta1 integrin/extracellular matrix interactions in neural stem cells. We find high levels of beta1 integrin expression in the stem-cell containing regions of the embryonic CNS, with associated expression of the laminin alpha2 chain. Expression levels of laminin alpha2 are reduced in the postnatal CNS, but a population of cells expressing high levels of beta1 remains. Using neurospheres - aggregate cultures, derived from single stem cells, that have a three-dimensional architecture that results in the localisation. of the stem cell population around the edge of the sphere - we show directly that beta1 integrins are expressed at high levels on neural stem cells and can be used for their selection. MAPK, but not PI3K, signalling is required for neural stem cell maintenance, as assessed by neurosphere formation, and inhibition or genetic ablation of beta1 integrin using cre/lox technology reduces the level of MAPK activity. We conclude that integrins are therefore an important part of the signalling mechanisms that control neural stem cell behaviour in specific areas of the CNS.