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

A random cell motility gradient downstream of FGF controls elongation of an amniote embryo.
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DOI:
10.1038/nature09151
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发表时间:
2010-07-08
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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脊椎动物胚胎的特征在于伸长的前后(AP)体轴,其通过胚胎中后部生长区的进行性细胞沉积形成。在这里,我们使用组织消融在鸡胚证明,尾前体中胚层(PSM)轴伸长中起着关键作用。使用延时显微镜,我们分析了荧光标记的细胞在胚胎伸长过程中的PSM的运动,揭示了一个明确的后到前的细胞运动和方向性的梯度在PSM。我们跟踪PSM细胞外基质与标记细胞平行的运动,并从细胞的全局运动中减去细胞外基质的运动。相减后,细胞运动性保持分级,但缺乏方向性,表明与PSM中轴伸长相关的后部细胞运动不是内在的,而是反映组织变形。沿着PSM的细胞运动的梯度沿着与成纤维细胞生长因子(FGF)/促分裂原活化蛋白激酶(MAPK)梯度平行,其已经涉及该组织中细胞运动的控制。成纤维细胞生长因子信号功能增强和丧失实验都会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)而不是细胞周期抑制剂处理的胚胎显示出较慢的轴伸长速率。我们建议,梯度的随机细胞运动下游的FGF信号在PSM控制后伸长的胚胎。我们的数据表明,组织伸长是一个新兴的属性,产生于集体调控的分级,随机细胞运动,而不是由个别细胞运动的方向性的调节。
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) plays 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 suggest 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.
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影响因子: 11.1
作者:
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