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A random cell motility gradient downstream of FGF controls elongation of an amniote embryo

机译:FGF下游的随机细胞运动梯度控制着羊膜胚胎的伸长

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摘要

Vertebrate embryos are characterized by an elongated antero-posterior (AP) body axis, which forms by progressive cell deposition from a posterior growth zone in the embryo. Here, we used tissue ablation in the chicken embryo to demonstrate that the caudal presomitic mesoderm (PSM) has a key role in axis elongation. Using time-lapse microscopy, we analysed the movements of fluorescently labelled cells in the PSM during embryo elongation, which revealed a clear posterior-to-anterior gradient of cell motility and directionality in the PSM. We tracked the movement of the PSM extracellular matrix in parallel with the labelled cells and subtracted the extracellular matrix movement from the global motion of cells. After subtraction, cell motility remained graded but lacked directionality, indicating that the posterior cell movements associated with axis elongation in the PSM are not intrinsic but reflect tissue deformation. The gradient of cell motion along the PSM parallels the fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK) gradient, which has been implicated in the control of cell motility in this tissue. Both FGF signalling gain- and loss-of-function experiments lead to disruption of the motility gradient and a slowing down of axis elongation. Furthermore, embryos treated with cell movement inhibitors (blebbistatin or RhoK inhibitor), but not cell cycle inhibitors, show a slower axis elongation rate. We propose that the gradient of random cell motility downstream of FGF signalling in the PSM controls posterior elongation in the amniote embryo. Our data indicate that tissue elongation is an emergent property that arises from the collective regulation of graded, random cell motion rather than by the regulation of directionality of individual cellular movements.
机译:脊椎动物胚胎的特征是前后细长(AP)的身体轴,它是通过从胚胎后部生长区进行的渐进性细胞沉积形成的。在这里,我们在鸡胚中使用组织消融术来证明尾部早熟中胚层(PSM)在轴伸长中具有关键作用。使用延时显微镜,我们分析了胚胎伸长过程中PSM中荧光标记细胞的运动,揭示了PSM中细胞运动性和方向性的从前到后的明显梯度。我们跟踪与标记的细胞平行的PSM细胞外基质的运动,并从细胞的整体运动中减去细胞外基质的运动。减去后,细胞运动保持分级,但缺乏方向性,表明与PSM中轴伸长相关的后细胞运动不是固有的,而是反映组织变形。沿着PSM的细胞运动梯度与成纤维细胞生长因子(FGF)/有丝分裂原激活的蛋白激酶(MAPK)梯度平行,这与该组织中细胞运动的控制有关。 FGF信号传导功能丧失和丧失的实验均导致运动梯度的破坏和轴伸长的减慢。此外,用细胞运动抑制剂(blebbistatin或RhoK抑制剂)而非细胞周期抑制剂处理的胚胎显示出较慢的轴伸长率。我们建议在PSM中FGF信号下游的随机细胞运动梯度控制羊膜胚胎的后延伸。我们的数据表明组织伸长是一种新兴的属性,它是由梯度随机细胞运动的集体调节而不是由单个细胞运动的方向性调节引起的。

著录项

  • 来源
    《Nature》 |2010年第7303期|P.248-252|共5页
  • 作者单位

    Howard Hughes Medical Institute, Kansas City, Missouri 64110, USA Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), CNRS (UMR 7104), Inserm U964, Universite de Strasbourg, Illkirch F-67400, France;

    rnCenter for Studies in Physics and Biology, The Rockefeller University, New York, New York 10065, USA;

    rnCentre for Mathematical Biology, Mathematical Institute, University of Oxford, 24-29 St Giles, Oxford OX1 3LB, UK;

    rnStowers Institute for Medical Research, Kansas City, Missouri 64110, USA lnstitut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), CNRS (UMR 7104), Inserm U964, Universite de Strasbourg, Illkirch F-67400, France;

    rnDepartment of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA;

    rnHoward Hughes Medical Institute, Kansas City, Missouri 64110, USA Stowers Institute for Medical Research, Kansas City, Missouri 64110, USA lnstitut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), CNRS (UMR 7104), Inserm U964, Universite de Strasbourg, Illkirch F-67400, France Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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