title: In vivo confinement promotes collective migration of neural crest cells.
abstract: Collective cell migration is fundamental throughout development and in many diseases. Spatial confinement using micropatterns has been shown to promote collective cell migration in vitro, but its effect in vivo remains unclear. Combining computational and experimental approaches, we show that the in vivo collective migration of neural crest cells (NCCs) depends on such confinement. We demonstrate that confinement may be imposed by the spatiotemporal distribution of a nonpermissive substrate provided by versican, an extracellular matrix molecule previously proposed to have contrasting roles: barrier or promoter of NCC migration. We resolve the controversy by demonstrating that versican works as an inhibitor of NCC migration and also acts as a guiding cue by forming exclusionary boundaries. Our model predicts an optimal number of cells in a given confinement width to allow for directional migration. This optimum coincides with the width of neural crest migratory streams analyzed across different species, proposing an explanation for the highly conserved nature of NCC streams during development.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.
authors.forename: András
authors.initials: A
authors.lastname: Szabó
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.
authors.forename: Manuela
authors.initials: M
authors.lastname: Melchionda
authors.affiliation: Department of Biochemical and Dental Sciences and Morphofunctional Images, School of Medicine, University of Messina, 98122 Messina, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Nastasi
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.
authors.forename: Mae L
authors.initials: ML
authors.lastname: Woods
authors.affiliation: Department of Biochemical and Dental Sciences and Morphofunctional Images, School of Medicine, University of Messina, 98122 Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Campo
authors.affiliation: Center for Molecular and Translational Oncology, University of Parma, 43121 Parma, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Perris
authors.affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK r.mayor@ucl.ac.uk.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mayor
mesh_terms: D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003198:Computer Simulation; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D008954:Models, Biological; D009432:Neural Crest / Q000166:cytology* / Q000187:drug effects; D059008:Time-Lapse Imaging; D053675:Versicans / Q000494:pharmacology; D014981:Xenopus
chemical_list: D005353:Fibronectins; D053675:Versicans