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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis
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FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis

机译：FGF4和FGF8包含控制体发生的波前活性

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Somites form along the embryonic axis by sequential segmentation from the presomitic mesoderm (PSM) and differentiate into the segmented vertebral column as well as other unsegmented tissues. Somites are thought to form via the intersection of two activities known as the clock and the wavefront. Previous work has suggested that fibroblast growth factor (FGF) activity may be the wavefront signal, which maintains the PSM in an undifferen-tiated state. However, it is unclear which (if any) of the FGFs expressed in the PSM comprise this activity, as removal of any one gene is insufficient to disrupt early somitogenesis. Here we show that when both Fgf4 and Fgf8 are deleted in the PSM, expression of most PSM genes is absent, including cycling genes, WNT pathway genes, and markers of undifferentiated PSM. Significantly, markers of nascent somite cell fate expand throughout the PSM, demonstrating the premature differentiation of this entire tissue, a highly unusual phenotype indicative of the loss of wavefront activity. When WNT signaling is restored in mutants, PSM progenitor markers are partially restored but premature differentiation of the PSM still occurs, demonstrating that FGF signaling operates independently of WNT signaling. This study provides genetic evidence that FGFs are the wavefront signal and identifies the specific FGF ligands that encode this activity. Furthermore, these data show that FGF action maintains WNT signaling, and that both signaling pathways are required in parallel to maintain PSM progenitor tissue.
机译：通过从早熟中胚层（PSM）进行顺序分割，沿着胚轴形成体节，并分化为分割的椎骨柱和其他未分割的组织。人们认为苏米特人是通过两个活动的交集形成的，这两个活动被称为时钟和波前。先前的工作表明成纤维细胞生长因子（FGF）的活性可能是波前信号，它将PSM保持在未分化状态。但是，尚不清楚PSM中表达的哪些FGF（如果有的话）具有这种活性，因为去除任何一个基因不足以破坏早期的体细胞生成。在这里，我们显示当Fgf4和Fgf8都在PSM中缺失时，大多数PSM基因都不存在，包括循环基因，WNT通路基因和未分化PSM的标记。值得注意的是，新生体细胞命运的标志物在整个PSM中扩展，表明了整个组织的过早分化，这是一种非常不寻常的表型，表明波阵面活动的丧失。当WNT信号在突变体中恢复后，PSM祖细胞标志物会部分恢复，但PSM仍会过早分化，这表明FGF信号独立于WNT信号运行。这项研究提供了FGFs是波前信号的遗传证据，并鉴定了编码该活性的特定FGF配体。此外，这些数据表明FGF作用维持了WNT信号传导，并且并行需要两条信号传导路径来维持PSM祖细胞。

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