Polarization and migration in the zebrafish posterior lateral line system

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning*
  • Cell Movement*
  • Cell Polarity*
  • Computational Biology
  • Models, Biological
  • Zebrafish / embryology*

Grants and funding

The research was supported by a fellowship grant from the Canadian Breast Cancer Foundation - BC/Yukon Region to HK (http://www.cbcf.org/bc/YourDollarAtWork/fellowships/Pages/default.aspx), a Discovery Grant from the Natural Science and Engineering Research Council of Canada [RGPIN-41870-12] to LEK, CZ and DB, [RGPIN-2016-04625] to EP (http://www.nserc-crsng.gc.ca/NSERC-CRSNG/Index_eng.asp), and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HD001012-15] to ABC and DDN (https://www.nichd.nih.gov/grants-funding/Pages/default.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.