BACKGROUND Most oligodendrocytes of the spinal cord originate from ventral progenitor cells of the pMN domain, characterized by expression of the transcription factor Olig2. A minority of oligodendrocytes is also recognized to emerge from dorsal progenitors during fetal development. The prevailing view is that generation of ventral oligodendrocytes depends on Sonic hedgehog (Shh) while dorsal oligodendrocytes develop under the influence of Fibroblast Growth Factors (FGFs). RESULTS Using the well-established model of the chicken embryo, we show that ventral spinal progenitor cells activate FGF signaling at the onset of oligodendrocyte precursor cell (OPC) generation. Inhibition of FGF receptors at that time appears sufficient to prevent generation of ventral OPCs, highlighting that, in addition to Shh, FGF signaling is required also for generation of ventral OPCs. We further reveal an unsuspected interplay between Shh and FGF signaling by showing that FGFs serve dual essential functions in ventral OPC specification. FGFs are responsible for timely induction of a secondary Shh signaling center, the lateral floor plate, a crucial step to create the burst of Shh required for OPC specification. At the same time, FGFs prevent down-regulation of Olig2 in pMN progenitor cells as these cells receive higher threshold of the Shh signal. Finally, we bring arguments favoring a key role of newly differentiated neurons acting as providers of the FGF signal required to trigger OPC generation in the ventral spinal cord. CONCLUSION Altogether our data reveal that the FGF signaling pathway is activated and required for OPC commitment in the ventral spinal cord. More generally, our data may prove important in defining strategies to produce large populations of determined oligodendrocyte precursor cells from undetermined neural progenitors, including stem cells. In the long run, these new data could be useful in attempts to stimulate the oligodendrocyte fate in residing neural stem cells.

中文翻译：

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FGF信号控制腹侧脊髓中Shh依赖的少突胶质命运。

背景技术脊髓的大多数少突胶质细胞起源于pMN结构域的腹祖细胞，其特征在于转录因子Olig2的表达。在胎儿发育过程中，少数少突胶质细胞也被认为从背祖细胞中出现。普遍的观点是，腹侧少突胶质细胞的产生取决于声波刺猬（Shh），而背侧少突胶质细胞则在成纤维细胞生长因子（FGFs）的影响下发育。结果使用成熟的鸡胚模型，我们显示腹侧脊柱祖细胞在少突胶质前体细胞（OPC）生成开始时激活FGF信号传导。当时对FGF受体的抑制作用似乎足以阻止腹侧OPC的产生，这突出表明，除了Shh，产生腹侧OPCs也需要FGF信号传导。我们通过揭示FGFs在腹侧OPC规范中具有双重基本功能，进一步揭示了Shh和FGF信号之间的相互作用。FGF负责及时诱导次要Shh信号传导中心，即侧向底板，这是产生OPC规格所需的Shh爆发的关键步骤。同时，FGF阻止pMN祖细胞中Olig2的下调，因为这些细胞接受更高的Shh信号阈值。最后，我们提出了一些观点，这些观点赞成新分化的神经元在触发腹侧脊髓中OPC生成所需的FGF信号提供者中起关键作用。结论总的来说，我们的数据表明FGF信号通路被激活，并且是腹侧脊髓中OPC参与所必需的。更普遍地说，我们的数据可能在确定策略中具有重要意义，该策略可用于从不确定的神经祖细胞（包括干细胞）中产生大量确定的少突胶质前体细胞。从长远来看，这些新数据可能有助于刺激少突胶质细胞在驻留神经干细胞中的命运。