The cerebrospinal fluid provides a proliferative niche for neural progenitor cells.
The cerebrospinal fluid provides a proliferative niche for neural progenitor cells.
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DOI：
10.1016/j.neuron.2011.01.023
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发表时间：
2011-03-10
期刊：
影响因子：
16.2
通讯作者：
Walsh CA
中科院分区：
文献类型：
--
作者：
Lehtinen MK;Zappaterra MW;Chen X;Yang YJ;Hill AD;Lun M;Maynard T;Gonzalez D;Kim S;Ye P;D'Ercole AJ;Wong ET;LaMantia AS;Walsh CA
皮质发育依赖于细胞自主和外在线索的积极整合，但这些过程的协调知之甚少。在这里，我们表明，顶端复合蛋白Pals1和Pten有相反的作用，在本地化的Igf1R的顶端，脑皮质祖细胞的脑室域。我们发现，脑脊液（CSF），接触这个顶端域，有一个年龄依赖性的增殖，其中大部分是由于IgF2的影响，但CSF中含有其他信号活动以及。多形性胶质母细胞瘤患者的CSF样本显示Igf2升高，并以Igf2依赖性方式刺激干细胞增殖。总之，我们的研究结果表明，顶端复合体耦合了内在和外在信号，使祖细胞能够感知广泛分布在整个大脑中的可扩散的CSF传播信号并做出适当的反应。CSF成分的时间控制可能与正常发育和神经病理学状况具有关键相关性。
Cortical development depends on the active integration of cell autonomous and extrinsic cues, but the coordination of these processes is poorly understood. Here, we show that the apical complex protein Pals1 and Pten have opposing roles in localizing the Igf1R to the apical, ventricular domain of cerebral cortical progenitor cells. We found that the cerebrospinal fluid (CSF), which contacts this apical domain, has an age-dependent effect on proliferation, much of which is attributable to Igf2, but that CSF contains other signaling activities as well. CSF samples from patients with glioblastoma multiforme show elevated Igf2 and stimulate stem cell proliferation in an Igf2-dependent manner. Together, our findings demonstrate that the apical complex couples intrinsic and extrinsic signaling, enabling progenitors to sense and respond appropriately to diffusible CSF-borne signals distributed widely throughout the brain. The temporal control of CSF composition may have critical relevance to normal development and neuropathological conditions.