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Leader cell positioning drives wound-directed collective migration in TGFβ-stimulated epithelial sheets

During wound healing and cancer metastasis, cells are frequently observed to migrate in collective groups. This mode of migration relies on the cooperative guidance of leader and follower cells throughout the collective group. The upstream determinants and molecular mechanisms behind such cellular g...

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Autores principales: Chapnick, Douglas A., Liu, Xuedong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019490/
https://www.ncbi.nlm.nih.gov/pubmed/24623725
http://dx.doi.org/10.1091/mbc.E14-01-0697
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author Chapnick, Douglas A.
Liu, Xuedong
author_facet Chapnick, Douglas A.
Liu, Xuedong
author_sort Chapnick, Douglas A.
collection PubMed
description During wound healing and cancer metastasis, cells are frequently observed to migrate in collective groups. This mode of migration relies on the cooperative guidance of leader and follower cells throughout the collective group. The upstream determinants and molecular mechanisms behind such cellular guidance remain poorly understood. We use live-cell imaging to track the behavior of epithelial sheets of keratinocytes in response to transforming growth factor β (TGFβ), which stimulates collective migration primarily through extracellular regulated kinase 1/2 (Erk1/2) activation. TGFβ-treated sheets display a spatial pattern of Erk1/2 activation in which the highest levels of Erk1/2 activity are concentrated toward the leading edge of a sheet. We show that Erk1/2 activity is modulated by cellular density and that this functional relationship drives the formation of patterns of Erk1/2 activity throughout sheets. In addition, we determine that a spatially constrained pattern of Erk1/2 activity results in collective migration that is primarily wound directed. Conversely, global elevation of Erk1/2 throughout sheets leads to stochastically directed collective migration throughout sheets. Our study highlights how the spatial patterning of leader cells (cells with elevated Erk1/2 activity) can influence the guidance of a collective group of cells during wound healing.
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spelling pubmed-40194902014-07-30 Leader cell positioning drives wound-directed collective migration in TGFβ-stimulated epithelial sheets Chapnick, Douglas A. Liu, Xuedong Mol Biol Cell Articles During wound healing and cancer metastasis, cells are frequently observed to migrate in collective groups. This mode of migration relies on the cooperative guidance of leader and follower cells throughout the collective group. The upstream determinants and molecular mechanisms behind such cellular guidance remain poorly understood. We use live-cell imaging to track the behavior of epithelial sheets of keratinocytes in response to transforming growth factor β (TGFβ), which stimulates collective migration primarily through extracellular regulated kinase 1/2 (Erk1/2) activation. TGFβ-treated sheets display a spatial pattern of Erk1/2 activation in which the highest levels of Erk1/2 activity are concentrated toward the leading edge of a sheet. We show that Erk1/2 activity is modulated by cellular density and that this functional relationship drives the formation of patterns of Erk1/2 activity throughout sheets. In addition, we determine that a spatially constrained pattern of Erk1/2 activity results in collective migration that is primarily wound directed. Conversely, global elevation of Erk1/2 throughout sheets leads to stochastically directed collective migration throughout sheets. Our study highlights how the spatial patterning of leader cells (cells with elevated Erk1/2 activity) can influence the guidance of a collective group of cells during wound healing. The American Society for Cell Biology 2014-05-15 /pmc/articles/PMC4019490/ /pubmed/24623725 http://dx.doi.org/10.1091/mbc.E14-01-0697 Text en © 2014 Chapnick and Liu. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Chapnick, Douglas A.
Liu, Xuedong
Leader cell positioning drives wound-directed collective migration in TGFβ-stimulated epithelial sheets
title Leader cell positioning drives wound-directed collective migration in TGFβ-stimulated epithelial sheets
title_full Leader cell positioning drives wound-directed collective migration in TGFβ-stimulated epithelial sheets
title_fullStr Leader cell positioning drives wound-directed collective migration in TGFβ-stimulated epithelial sheets
title_full_unstemmed Leader cell positioning drives wound-directed collective migration in TGFβ-stimulated epithelial sheets
title_short Leader cell positioning drives wound-directed collective migration in TGFβ-stimulated epithelial sheets
title_sort leader cell positioning drives wound-directed collective migration in tgfβ-stimulated epithelial sheets
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019490/
https://www.ncbi.nlm.nih.gov/pubmed/24623725
http://dx.doi.org/10.1091/mbc.E14-01-0697
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