Polarization and migration in the zebrafish posterior lateral line system

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

PLOS Computational Biology, 2017, vol. 13, issue 4, 1-26

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.Author summary: Collective migration of a group of cells plays an important role in the development of an organism. Here we study a specific example in the zebrafish embryo, where a group of about 100 cells (the posterior lateral line primordium, PLLP), destined to form sensory structures, migrates from head to tail. We model the process from the initial polarization to the migration, with a focus on how tissue polarity could arise. Using a 3D deformable-ellipsoid cell-based simulation, we explore the effects of cell-cell, cell-substrate, and cell-chemical interactions. We discuss drag forces experienced by cells and what that implies about the inherent active motion of both leading and trailing cells. The model allows us to test how each of several biological parameters affects the shape, size, effective migration and speed of migration. A subsequent study will be aimed at understanding the formation and deposition of neuromasts.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1005451

DOI: 10.1371/journal.pcbi.1005451

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