Division of Genetics, Howard Hughes Medical Institute, Children's Hospital Boston, Boston, MA 02115, USA.
Neuron. 2011 Mar 10;69(5):893-905. doi: 10.1016/j.neuron.2011.01.023.
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.
皮质发育依赖于细胞自主和外在线索的积极整合，但这些过程的协调尚不清楚。在这里，我们表明顶端复合物蛋白 Pals1 和 Pten 在将 Igf1R 定位到大脑皮质祖细胞的顶端、室腔域中具有相反的作用。我们发现，与该顶端域接触的脑脊液（CSF）对增殖具有年龄依赖性影响，其中大部分归因于 Igf2，但 CSF 中也含有其他信号活性。来自多形性胶质母细胞瘤患者的 CSF 样本显示 Igf2 升高，并以 Igf2 依赖的方式刺激干细胞增殖。总之，我们的发现表明顶端复合物将内在和外在信号耦合在一起，使祖细胞能够感知并适当地响应广泛分布在大脑中的弥散 CSF 携带的信号。CSF 组成的时间控制可能对正常发育和神经病理学状况具有至关重要的意义。
