Diverse FGF receptor signaling controls astrocyte specification and proliferation
Diverse FGF receptor signaling controls astrocyte specification and proliferation
复制标题
DOI：
10.1016/j.bbrc.2010.03.174
复制
发表时间：
2010-05-07
影响因子：
3.1
通讯作者：
Song, Mi-Ryoung
中科院分区：
文献类型：
--
作者：
Kang, Kyungjun;Song, Mi-Ryoung
在中枢神经系统发育过程中，多能神经前体细胞陆续分化为神经元和神经胶质细胞。成纤维细胞生长因子-2(成纤维细胞生长因子-2)是维持神经前体细胞处于未分化状态的主要信号，也被认为影响从神经发生到胶质形成的转变。在这里，我们提出的证据是，成纤维细胞生长因子受体和潜在的信号通路传递成纤维细胞生长因子-2信号，除了有丝分裂活性外，还调节星形胶质细胞的规格。应用成纤维细胞生长因子-2抑制神经发生，而在体外用FGFR拮抗剂处理则促进神经发生。将带有突变酪氨酸残基的嵌合FGFRs导入皮质前体细胞和药物治疗以特异性阻断个别下游信号通路表明，FGFR的整体活性而不是个别的自磷酸化位点对于传递神经胶质指定的信号是重要的。相反，FGFR促进细胞增殖的信号主要通过MAPK途径传递。综上所述，我们的研究结果表明，FGFR活性促进了发育中的中枢神经系统星形胶质细胞的规范。(C)2010 Elsevier Inc.保留所有权利。
During CNS development, pluripotency neuronal progenitor cells give rise in succession to neurons and glia. Fibroblast growth factor-2 (FGF-2), a major signal that maintains neural progenitors in the undifferentiated state, is also thought to influence the transition from neurogenesis to gliogenesis. Here we present evidence that FGF receptors and underlying signaling pathways transmit the FGF-2 signals that regulate astrocyte specification aside from its mitogenic activity. Application of FGF-2 to cortical progenitors suppressed neurogenesis whereas treatment with an FGFR antagonist in vitro promoted neurogenesis. Introduction of chimeric FGFRs with mutated tyrosine residues into cortical progenitors and drug treatments to specifically block individual downstream signaling pathways revealed that the overall activity of FGFR rather than individual autophosphorylation sites is important for delivering signals for glial specification. In contrast, a signal for cell proliferation by FGFR was mainly delivered by MAPK pathway. Together our findings indicate that FGFR activity promotes astrocyte specification in the developing CNS. (C) 2010 Elsevier Inc. All rights reserved.