Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration
- University of Oxford, United Kingdom
- Children's Mercy Kansas City, United States
- Stowers Institute for Medical Research, United States
- University of Pittsburgh, United States
Abstract
Collective cell migration plays an essential role in vertebrate development, yet the extent to which dynamically changing microenvironments influence this phenomenon remains unclear. Observations of the distribution of the extracellular matrix (ECM) component fibronectin during the migration of loosely connected neural crest cells (NCCs) lead us to hypothesize that NCC remodeling of an initially punctate ECM creates a scaffold for trailing cells, enabling them to form robust and coherent stream patterns. We evaluate this idea in a theoretical setting by developing an individual-based computational model that incorporates reciprocal interactions between NCCs and their ECM. ECM remodeling, haptotaxis, contact guidance, and cell-cell repulsion are sufficient for cells to establish streams in silico, however additional mechanisms, such as chemotaxis, are required to consistently guide cells along the correct target corridor. Further model investigations imply that contact guidance and differential cell-cell repulsion between leader and follower cells are key contributors to robust collective cell migration by preventing stream breakage. Global sensitivity analysis and simulated gain- and loss-of-function experiments suggest that long-distance migration without jamming is most likely to occur when leading cells specialize in creating ECM fibers, and trailing cells specialize in responding to environmental cues by upregulating mechanisms such as contact guidance.
Data availability
All data from the mathematical model have been deposited in Dryad (https://doi.org/10.5061/dryad.69p8cz958). Software used for the mathematical model is available on Github at the following link: https://github.com/wdmartinson/Neural_Crest_Project.
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Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration - Mathematical Model ResultsDryad Digital Repository, doi:10.5061/dryad.69p8cz958.
Article and author information
Author details
William Duncan Martinson
Funding
European Research Council (883363)
- William Duncan Martinson
University of Oxford
- William Duncan Martinson
Keasbey Memorial Foundation
- William Duncan Martinson
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37 HD044750 and R21 HD106629)
- Lance A Davidson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Stacey D Finley, University of Southern California, United States
Ethics
Animal experimentation: Our work did involve animal experimentation subject to ethical guidelines and according to the approved protocol IBC-2003-23-pmk.All of our chick embryology experiments were performed during the first week of development (<7 days; Hamburger and Hamilton (1951) Stages 11-16). This is significantly shorter in time than 2/3 (14days) to normal hatching (21 days). Thus, we do not describe a measure of euthanasia to avoid pain. In order to prevent incubated eggs from developing to hatching, all batches of eggs are labeled by the user with the date of the start of incubation and all incubators are checked weekly to remove eggs older than 7 days. Should the situation arise whereby an egg hatches, end of life is carried out by immediate decapitation.
Version history
- Preprint posted: September 16, 2022 (view preprint)
- Received: September 29, 2022
- Accepted: April 13, 2023
- Accepted Manuscript published: April 19, 2023 (version 1)
- Version of Record published: May 19, 2023 (version 2)
Copyright
© 2023, Martinson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Dynamic fibronectin assembly and remodeling by leader neural crest cells prevents jamming in collective cell migration
eLife 12:e83792.
https://doi.org/10.7554/eLife.83792
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