A chemo-mechanical model of endoderm movements driving elongation of the amniote hindgut.

A chemo-mechanical model of endoderm movements driving elongation of the amniote hindgut.
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DOI:
10.1242/dev.202010
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发表时间:
2023-11-15
期刊:
Development (Cambridge, England)
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虽然机械和生物化学的发展描述是必不可少的,整合上游形态发生线索与下游组织力学仍然在脊椎动物形态发生研究不足。在这里,我们开发了一个二维的化学机械模型来研究如何内胚层的机械性能和成纤维细胞生长因子(FGF)的运输性能调节禽后肠形态发生在一个协调的方式。后内胚层细胞将FGF配体的梯度转化为收缩力梯度,导致力不平衡,从而驱动集体细胞运动,从而延长形成的后肠管。我们制定了一个2D反应扩散平流模型描述的FGF蛋白梯度的形成作为后移位的细胞转录不稳定的Fgf8 mRNA在轴伸长,加上翻译,扩散和降解的FGF蛋白。内胚层被建模为活性粘性流体,其产生与FGF浓度成比例的收缩应力。参数值受实验数据的约束,该模型复制后肠形态发生的关键方面,表明分级各向同性收缩足以产生大的各向异性细胞运动,并提供了新的见解如何化学机械耦合跨中胚层和内胚层协调后肠伸长与轴伸长。总结:建立数学模型,研究鸡胚后肠形态发生的细胞集体运动中形态梯度和组织力学之间的相互作用。
Although mechanical and biochemical descriptions of development are each essential, integration of upstream morphogenic cues with downstream tissue mechanics remains understudied during vertebrate morphogenesis. Here, we developed a two-dimensional chemo-mechanical model to investigate how mechanical properties of the endoderm and transport properties of fibroblast growth factor (FGF) regulate avian hindgut morphogenesis in a coordinated manner. Posterior endoderm cells convert a gradient of FGF ligands into a contractile force gradient, leading to a force imbalance that drives collective cell movements that elongate the forming hindgut tube. We formulated a 2D reaction-diffusion-advection model describing the formation of an FGF protein gradient as a result of posterior displacement of cells transcribing unstable Fgf8 mRNA during axis elongation, coupled with translation, diffusion and degradation of FGF protein. The endoderm was modeled as an active viscous fluid that generates contractile stresses in proportion to FGF concentration. With parameter values constrained by experimental data, the model replicates key aspects of hindgut morphogenesis, suggests that graded isotropic contraction is sufficient to generate large anisotropic cell movements, and provides new insight into how chemo-mechanical coupling across the mesoderm and endoderm coordinates hindgut elongation with axis elongation. Summary: Formulation of a mathematical model to investigate the interplay between morphogen gradients and tissue mechanics in regulating the collective cell movements that drive hindgut morphogenesis in the chick embryo.
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