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斑马鱼后侧线系统中的极化与迁移

Polarization and migration in the zebrafish posterior lateral line system.

作者信息

Knutsdottir Hildur, Zmurchok Cole, Bhaskar Dhananjay, Palsson Eirikur, Dalle Nogare Damian, Chitnis Ajay B, Edelstein-Keshet Leah

机构信息

Department of Mathematics, University of British Columbia, Vancouver, British Columbia, Canada.

Department of Biology, Simon Fraser University, Burnaby, British Columbia, Canada.

出版信息

PLoS Comput Biol. 2017 Apr 3;13(4):e1005451. doi: 10.1371/journal.pcbi.1005451. eCollection 2017 Apr.

Abstract

Collective cell migration plays an important role in development. Here, we study the posterior lateral line primordium (PLLP) a group of about 100 cells, destined to form sensory structures, that migrates from head to tail in the zebrafish embryo. We model mutually inhibitory FGF-Wnt signalling network in the PLLP and link tissue subdivision (Wnt receptor and FGF receptor activity domains) to receptor-ligand parameters. We then use a 3D cell-based simulation with realistic cell-cell adhesion, interaction forces, and chemotaxis. Our model is able to reproduce experimentally observed motility with leading cells migrating up a gradient of CXCL12a, and trailing (FGF receptor active) cells moving actively by chemotaxis towards FGF ligand secreted by the leading cells. The 3D simulation framework, combined with experiments, allows an investigation of the role of cell division, chemotaxis, adhesion, and other parameters on the shape and speed of the PLLP. The 3D model demonstrates reasonable behaviour of control as well as mutant phenotypes.

摘要

集体细胞迁移在发育过程中起着重要作用。在此,我们研究斑马鱼胚胎中后外侧线原基(PLLP),这是一组约100个细胞,注定会形成感觉结构,并从头部向尾部迁移。我们对PLLP中相互抑制的FGF-Wnt信号网络进行建模,并将组织细分(Wnt受体和FGF受体活性域)与受体-配体参数联系起来。然后,我们使用基于细胞的3D模拟,该模拟具有逼真的细胞间粘附、相互作用力和趋化性。我们的模型能够重现实验观察到的运动性,即领先细胞沿CXCL12a梯度向上迁移,而尾随(FGF受体活性)细胞通过趋化作用向领先细胞分泌的FGF配体主动移动。3D模拟框架与实验相结合,使得能够研究细胞分裂、趋化性、粘附和其他参数对PLLP形状和速度的作用。3D模型展示了对照以及突变体表型的合理行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ffd/5393887/63d907a78bd2/pcbi.1005451.g001.jpg

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