Notch1-Dll4 signalling and mechanical force regulate leader cell formation during collective cell migration

Reza Riahi, Jian Sun, Shue Wang, Min Long, Donna D. Zhang, Pak Kin Wong

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

At the onset of collective cell migration, a subset of cells within an initially homogenous population acquires a distinct 'leader' phenotype with characteristic morphology and motility. However, the factors driving the leader cell formation as well as the mechanisms regulating leader cell density during the migration process remain to be determined. Here we use single-cell gene expression analysis and computational modelling to show that the leader cell identity is dynamically regulated by Dll4 signalling through both Notch1 and cellular stress in a migrating epithelium. Time-lapse microscopy reveals that Dll4 is induced in leader cells after the creation of the cell-free region and leader cells are regulated via Notch1-Dll4 lateral inhibition. Furthermore, mechanical stress inhibits Dll4 expression and leader cell formation in the monolayer. Collectively, our findings suggest that a reduction of mechanical force near the boundary promotes Notch1-Dll4 signalling to dynamically regulate the density of leader cells during collective cell migration.

Original languageEnglish (US)
Article number6556
JournalNature communications
Volume6
DOIs
StatePublished - 2015

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Cell Movement
cells
Gene expression
Monolayers
Microscopic examination
Cell Count
Mechanical Stress
Microscopy
phenotype
locomotion
Epithelium
epithelium
gene expression
Phenotype
Gene Expression
set theory
Population
microscopy

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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title = "Notch1-Dll4 signalling and mechanical force regulate leader cell formation during collective cell migration",
abstract = "At the onset of collective cell migration, a subset of cells within an initially homogenous population acquires a distinct 'leader' phenotype with characteristic morphology and motility. However, the factors driving the leader cell formation as well as the mechanisms regulating leader cell density during the migration process remain to be determined. Here we use single-cell gene expression analysis and computational modelling to show that the leader cell identity is dynamically regulated by Dll4 signalling through both Notch1 and cellular stress in a migrating epithelium. Time-lapse microscopy reveals that Dll4 is induced in leader cells after the creation of the cell-free region and leader cells are regulated via Notch1-Dll4 lateral inhibition. Furthermore, mechanical stress inhibits Dll4 expression and leader cell formation in the monolayer. Collectively, our findings suggest that a reduction of mechanical force near the boundary promotes Notch1-Dll4 signalling to dynamically regulate the density of leader cells during collective cell migration.",
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Notch1-Dll4 signalling and mechanical force regulate leader cell formation during collective cell migration. / Riahi, Reza; Sun, Jian; Wang, Shue; Long, Min; Zhang, Donna D.; Wong, Pak Kin.

In: Nature communications, Vol. 6, 6556, 2015.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Sun, Jian

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AU - Long, Min

AU - Zhang, Donna D.

AU - Wong, Pak Kin

PY - 2015

Y1 - 2015

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