Directional tissue migration through a self-generated chemokine gradient.

Area of Science:

• Developmental Biology
• Cell Biology
• Molecular Biology

Background:

• Embryogenesis relies on directed cell migration, typically along external chemoattractant gradients.
• Self-generation of local, traveling gradients offers an alternative migration strategy, enabling self-determined directionality.
• In vivo visualization of endogenous guidance cues has been a major limitation in studying self-generated gradients.

Purpose of the Study:

• To define the in vivo dynamics of the chemokine Cxcl12a using a fluorescent timer approach.
• To demonstrate that migrating cell collectives can self-generate chemokine gradients in vivo.
• To provide in vivo proof for self-directed tissue migration via local extracellular cue shaping.

Main Methods:

• Utilized a fluorescent timer approach to measure ligand-triggered receptor turnover in living zebrafish.
• Applied this method to the zebrafish lateral line primordium model system.
• Engineered an external source of the atypical receptor Cxcr7 to test sufficiency of self-generated gradients.

Main Results:

• Quantified in vivo dynamics of the guidance molecule Cxcl12a.
• Showed that migrating cell collectives self-generate chemokine activity gradients through polarized receptor-mediated internalization.
• Demonstrated that a self-generated gradient mechanism is sufficient to direct robust collective cell migration.

Conclusions:

• This study provides the first in vivo evidence for self-directed tissue migration driven by local shaping of extracellular cues.
• The findings reveal a novel mechanism for collective cell migration independent of long-range gradients.
• Establishes a framework for investigating self-directed migration in developmental processes and diseases like cancer invasion.