Regulation of neural progenitor proliferation and survival by β1 integrins
Regulation of neural progenitor proliferation and survival by β1 integrins
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DOI：
10.1242/jcs.02396
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发表时间：
2005-06-15
影响因子：
4
通讯作者：
Suter, U
中科院分区：
文献类型：
--
作者：
Leone, DP;Relvas, JB;Suter, U
神经干细胞产生未分化的巢蛋白阳性祖细胞，其在分化成神经元和神经胶质细胞之前经历广泛的细胞分裂。这一过程的精确控制很可能是，至少在一定程度上，控制来自细胞外环境的指导线索。这些线索中的一些由细胞外基质受体的整合素家族解释。使用神经球细胞培养物作为模型系统，我们表明β 1-整合素信号在祖细胞增殖，存活和迁移的调节中起着至关重要的作用。在β 1-整联蛋白等位基因的条件性遗传消融和随后的β 1-整联蛋白细胞表面蛋白的损失之后，突变的巢蛋白阳性祖细胞比它们的野生型对应物增殖更少并且死亡数量更高。不同ECM基质上的突变祖细胞迁移也受损。这些影响可以通过添加外源性生长因子来部分补偿。因此，β 1-整联蛋白信号传导和生长因子信号传导紧密相互作用以控制巢蛋白阳性祖细胞的数量和迁移能力。
Neural stem cells give rise to undifferentiated nestin-positive progenitors that undergo extensive cell division before differentiating into neuronal and glial cells. The precise control of this process is likely to be, at least in part, controlled by instructive cues originating from the extracellular environment. Some of these cues are interpreted by the integrin family of extracellular matrix receptors. Using neurosphere cell cultures as a model system, we show that beta 1-integrin signalling plays a crucial role in the regulation of progenitor cell proliferation, survival and migration. Following conditional genetic ablation of the beta 1-integrin allele, and consequent loss of beta 1-integrin cell surface protein, mutant nestin-positive progenitor cells proliferate less and die in higher numbers than their wild-type counterparts. Mutant progenitor cell migration on different ECM substrates is also impaired. These effects can be partially compensated by the addition of exogenous growth factors. Thus, beta 1-integrin signalling and growth factor signalling tightly interact to control the number and migratory capacity of nestin-positive progenitor cells.