Fibroblast growth factor signaling is required for the generation of oligodendrocyte progenitors from the embryonic forebrain.
Fibroblast growth factor signaling is required for the generation of oligodendrocyte progenitors from the embryonic forebrain.
复制标题
成纤维细胞生长因子信号传导是从胚胎前脑中产生少突胶质细胞祖细胞所必需的。
DOI：
10.1523/jneurosci.4800-10.2011
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发表时间：
2011-03-30
期刊：
影响因子：
--
通讯作者：
Bansal R
中科院分区：
文献类型：
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作者：
Furusho M;Kaga Y;Ishii A;Hébert JM;Bansal R
成纤维细胞生长因子（FGF）包括与多种神经功能有关的发育调节因子家族。FGF受体-1、-2、-3（Fgfrs）在胚胎前脑中表达，包括与少突胶质细胞祖细胞（OLP）产生的腹侧位点重叠的区域。虽然已知FGF信号传导影响体外OLP的增殖，但缺乏体内不同Fgfr的功能。在这里，我们研究了单和双突变体与FGFRs的条件性破坏，特别是在胚胎前脑，研究的影响，FGF的生成和增殖的OLP在体内。FGF信号，通过Fgfr 1和Fgfr 2之间的合作，而不是Fgfr 3，是所需的初始生成的OLP在小鼠腹侧前脑，与Fgfr 1是一个更强的诱导剂比Fgfr 2。在源自胚胎突变前脑或在Fgfr抑制剂存在下生长的正常前脑的培养物中，观察到OLP产生的强烈减弱，这支持了FGF信号传导在体内的作用。与体外研究结果相反，体内OLP的增殖不需要Fgfr 1和Fgfr 2信号传导。最后，在FGFR突变体中发生OLP生成失败而不损失音刺猬（Shh）信号传导;并且在平行培养物中对FGFR或刺猬信号传导的药理学抑制强烈抑制OLP生成，表明Fgfrs与Shh合作生成OLP。总的来说，我们的研究结果首次揭示了FGF信号在体内的重要作用，其中三个Fgfrs差异控制胚胎腹侧前脑OLP的正常生成。
Fibroblast growth factors (FGFs) comprise a family of developmental regulators implicated in a wide variety of neurological functions. FGF receptors-1,-2,-3 (Fgfrs) are expressed in the embryonic forebrain, including regions overlapping with ventral sites of oligodendrocyte progenitor (OLP) generation. Although FGF signaling is known to influence the proliferation of OLPs in vitro, functions of different Fgfrs in vivo are lacking. Here, we examined single and double mutants with conditional disruption of Fgfrs, specifically in the embryonic forebrain, to investigate the effect of FGFs on the generation and proliferation of OLPs in vivo. FGF signaling, through cooperation between Fgfr1 and Fgfr2 but not Fgfr3, is required for the initial generation of OLPs in the mouse ventral forebrain, with Fgfr1 being a stronger inducer than Fgfr2. In cultures derived from embryonic mutant forebrains or from normal forebrains grown in the presence of Fgfr inhibitor, a strong attenuation of OLP generation was observed, supporting the role of FGF signaling in vivo. Contrary to in vitro findings, Fgfr1 and Fgfr2 signaling is not required for the proliferation of OLPs in vivo. Finally, failure of OLP generation in the Fgfr mutants occurred without loss of sonic hedgehog (Shh) signaling; and pharmacological inhibition of either Fgfr or hedgehog signaling in parallel cultures strongly inhibited OLP generation, suggesting that Fgfrs cooperate with Shh to generate OLPs. Overall, our results reveal for the first time an essential role of FGF signaling in vivo, where the three Fgfrs differentially control the normal generation of OLPs from the embryonic ventral forebrain.