Fgf4 maintains Hes7 levels critical for normal somite segmentation clock function.
Fgf4 maintains Hes7 levels critical for normal somite segmentation clock function.
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DOI：
10.7554/elife.55608
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发表时间：
2020-11-19
期刊：
影响因子：
7.7
通讯作者：
Lewandoski M
中科院分区：
文献类型：
--
作者：
Anderson MJ;Magidson V;Kageyama R;Lewandoski M
在脊椎动物发育过程中，体前中胚层（PSM）周期性地分裂成体，体将形成节段脊柱和相关的肌肉、结缔组织和真皮层。体细胞发生的周期性是由振荡Notch活性的分割时钟调节的。在这里，我们研究了仅缺乏Fgf4或Fgf8的小鼠突变体，我们之前证明了它们可以冗余地阻止PSM分化。Fgf8不是体细胞发生所必需的，但Fgf4突变体表现出一系列椎体缺陷。我们在基于imaris的体积组织亚群中，通过杂交链式反应定量mrna荧光标记来分析Fgf4突变体。这些数据表明FGF4维持Hes7水平和正常的振荡模式。为了支持FGF4通过Hes7调控体细胞发生的假设，我们证明了Hes7和FGF4之间的遗传协同作用，而不是与Fgf8。我们的数据表明，Fgf4在由Notch振荡缺陷引起的人类椎骨分割缺陷的频谱中具有潜在的重要作用。
During vertebrate development, the presomitic mesoderm (PSM) periodically segments into somites, which will form the segmented vertebral column and associated muscle, connective tissue, and dermis. The periodicity of somitogenesis is regulated by a segmentation clock of oscillating Notch activity. Here, we examined mouse mutants lacking only Fgf4 or Fgf8, which we previously demonstrated act redundantly to prevent PSM differentiation. Fgf8 is not required for somitogenesis, but Fgf4 mutants display a range of vertebral defects. We analyzed Fgf4 mutants by quantifying mRNAs fluorescently labeled by hybridization chain reaction within Imaris-based volumetric tissue subsets. These data indicate that FGF4 maintains Hes7 levels and normal oscillatory patterns. To support our hypothesis that FGF4 regulates somitogenesis through Hes7, we demonstrate genetic synergy between Hes7 and Fgf4, but not with Fgf8. Our data indicate that Fgf4 is potentially important in a spectrum of human Segmentation Defects of the Vertebrae caused by defective Notch oscillations.