The ciliary neurotrophic factor/leukemia inhibitory factor/gp130 receptor complex operates in the maintenance of mammalian forebrain neural stem cells
The ciliary neurotrophic factor/leukemia inhibitory factor/gp130 receptor complex operates in the maintenance of mammalian forebrain neural stem cells
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DOI：
10.1523/jneurosci.21-19-07642.2001
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发表时间：
2001-10-01
影响因子：
5.3
通讯作者：
Weiss, S
中科院分区：
文献类型：
--
作者：
Shimazaki, T;Shingo, T;Weiss, S
通过共同受体亚单位gp 130传递信号的细胞因子包括睫状神经营养因子（CNTF）、白细胞介素-6、白血病抑制因子（LIF）和制瘤素M，在CNS发育中具有多效性功能。由于限制性表达结构域的CNTF受体α（CNTFR）在发育中的前脑生发区和成人前脑脑室周围区，我们已经研究了假定的作用CNTFR/LIFR/gp 130介导的信号在体内和体外调节前脑神经干细胞的命运。对LIFR缺陷小鼠的分析表明，LIFR表达水平的降低导致成体神经干细胞数量的减少。在成年LIFR杂合子（+/-）小鼠，前脑室管膜下神经干细胞及其后代和嗅球TH免疫反应阳性神经元的数量显着减少。脑室内输注CNTF到成年小鼠前脑，在表皮生长因子（EGF）的存在或不存在，增强自我更新的神经干细胞在体内。EGF反应性神经干细胞在体外增殖的分析发现，CNTF抑制神经干细胞向胶质祖细胞的谱系限制，这反过来又导致干细胞数量的增加。这些结果表明，CNTFR/LIFR/gp 130介导的信号支持前脑神经干细胞的维持，可能是通过抑制限制神经胶质祖细胞的命运。
The cytokines that signal through the common receptor subunit gp130, including ciliary neurotrophic factor (CNTF), interleukin-6, leukemia inhibitory factor (LIF) and oncostatin M, have pleiotropic functions in CNS development. Given the restricted expression domain of the CNTF receptor alpha (CNTFR) in the developing forebrain germinal zone and adult forebrain periventricular area, we have examined the putative role of CNTFR/LIFR/gp130-mediated signaling in regulating forebrain neural stem cell fate in vivo and in vitro. Analysis of LIFR-deficient mice revealed that a decreased level of LIFR expression results in a reduction in the number of adult neural stem cells. In adult LIFR heterozygote (+/-) mice, the number of neural stem cells and their progeny in the forebrain subependyma and TH-immunoreactive neurons in the olfactory bulb were significantly reduced. Intraventricular infusion of CNTF into the adult mouse forebrain, in the absence or presence of epidermal growth factor (EGF), enhanced self-renewal of neural stem cells in vivo. Analyses of EGF-responsive neural stern cells proliferating in vitro found that CNTF inhibits lineage restriction of neural stem cells to glial progenitors, which in turn results in enhanced expansion of stem cell number. These results suggest that CNTFR/LIFR/gp130-mediated signaling supports the maintenance of forebrain neural stem cells, likely by suppressing restriction to a glial progenitor cell fate.