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首页> 外文期刊>Development >FGF8 acts as a classic diffusible morphogen to pattern the neocortex.
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FGF8 acts as a classic diffusible morphogen to pattern the neocortex.

机译：FGF8作为经典的可扩散形态发生剂，可为新皮质形成图案。

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Gain- and loss-of-function experiments have demonstrated that a source of fibroblast growth factor (FGF) 8 regulates anterior to posterior (A/P) patterning in the neocortical area map. Whether FGF8 controls patterning as a classic diffusible morphogen has not been directly tested. We report evidence that FGF8 diffuses through the mouse neocortical primordium from a discrete source in the anterior telencephalon, forms a protein gradient across the entire A/P extent of the primordium, and acts directly at a distance from its source to determine area identity. FGF8 immunofluorescence revealed FGF8 protein distributed in an A/P gradient. Fate-mapping experiments showed that outside the most anterior telencephalon, neocortical progenitor cells did not express Fgf8, nor were they derived from Fgf8-expressing cells, suggesting that graded distribution of FGF8 results from protein diffusion from the anterior source. Supporting this conclusion, a dominant-negative high-affinity FGF8 receptor captured endogenous FGF8 at a distance from the FGF8 source. New FGF8 sources introduced by electroporation showed haloes of FGF8 immunofluorescence indicative of FGF8 diffusion, and surrounding cells reacted to a new source of FGF8 by upregulating different FGF8-responsive genes in concentric domains around the source. Reducing endogenous FGF8 with the dominant-negative receptor in the central neocortical primordium induced cells to adopt a more posterior area identity, demonstrating long-range area patterning by FGF8. These observations support FGF8 as a classic diffusible morphogen in neocortex, thereby guiding future studies of neocortical pattern formation.
机译：功能获得和功能丧失实验已证明，成纤维细胞生长因子（FGF）8的来源可调节新皮层区域图中的从前到后（A / P）模式。 FGF8是否作为经典的可扩散形态发生因子控制图案形成尚未得到直接测试。我们报告的证据表明，FGF8通过小鼠新皮质原基从前端脑的离散来源扩散，在原基的整个A / P范围内形成蛋白质梯度，并直接作用于距其来源一定距离的区域，以确定区域身份。 FGF8免疫荧光显示FGF8蛋白以A / P梯度分布。命运图实验显示，在最前端脑外，新皮层祖细胞不表达Fgf8，也不来源于表达Fgf8的细胞，这表明FGF8的梯度分布是由前源的蛋白质扩散引起的。支持该结论的是，显性阴性高亲和力FGF8受体在距FGF8来源一定距离处捕获了内源性FGF8。通过电穿孔引入的新FGF8来源显示出FGF8免疫荧光的光环，表明FGF8扩散，周围细胞通过上调该来源周围同心域中的不同FGF8响应基因而与新的FGF8来源发生了反应。在中央新皮层原基诱导的细胞中用显性负受体还原内源性FGF8，以采用更后部的区域同一性，证明FGF8可以进行远距离区域构图。这些观察结果支持FGF8作为新皮质中的经典可扩散形态发生剂，从而指导了新皮质模式形成的未来研究。

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