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Notch1-Dll4 signalling and mechanical force regulate leader cell formation during collective cell migration
Reza Riahi1, Jian Sun1, Shue Wang1
1Department of Aerospace and Mechanical Engineering, The University of Arizona, Tucson, Arizona 85721-0119, USA.
Nature Communications
|March 14, 2015
Summary
Leader cell formation during collective cell migration is controlled by Dll4 (Delta-like 4) signaling. Mechanical stress and Notch1 (Notch 1) pathway interactions dynamically regulate leader cell density.
Area of Science:
- Cell Biology
- Developmental Biology
- Biophysics
Background:
- Collective cell migration is crucial for development and tissue repair.
- Leader cells initiate migration, but factors controlling their formation and density are unclear.
Purpose of the Study:
- To investigate the molecular mechanisms regulating leader cell formation and density.
- To understand the role of Dll4 signaling and mechanical stress in leader cell dynamics.
Main Methods:
- Single-cell gene expression analysis
- Computational modeling
- Time-lapse microscopy
Main Results:
- Dll4 (Delta-like 4) signaling, through Notch1 (Notch 1), regulates leader cell identity.
- Mechanical stress inhibits Dll4 expression and leader cell formation.
- Notch1-Dll4 lateral inhibition controls leader cells after creating a cell-free region.
Conclusions:
- Leader cell density is dynamically regulated by a balance between Dll4 signaling and mechanical forces.
- Reduced mechanical force at the boundary promotes leader cell formation via Notch1-Dll4 signaling.
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