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ZIRC
ZFIN ID: ZDB-PUB-131024-18
Directional tissue migration through a self-generated chemokine gradient
Donà, E., Barry, J.D., Valentin, G., Quirin, C., Khmelinskii, A., Kunze, A., Durdu, S., Newton, L.R., Fernandez-Minan, A., Huber, W., Knop, M., and Gilmour, D.
Date: 2013
Source: Nature   503(7475): 285-9 (Journal)
Registered Authors: Gilmour, Darren
Keywords: none
MeSH Terms:
  • Animals
  • Cell Movement/physiology*
  • Chemokine CXCL12/genetics
  • Chemokine CXCL12/metabolism
  • Chemotactic Factors/genetics
  • Chemotactic Factors/metabolism*
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Receptors, CXCR/genetics
  • Receptors, CXCR/metabolism
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 24067609 Full text @ Nature
FIGURES
ABSTRACT

The directed migration of cell collectives is a driving force of embryogenesis. The predominant view in the field is that cells in embryos navigate along pre-patterned chemoattractant gradients. One hypothetical way to free migrating collectives from the requirement of long-range gradients would be through the self-generation of local gradients that travel with them, a strategy that potentially allows self-determined directionality. However, a lack of tools for the visualization of endogenous guidance cues has prevented the demonstration of such self-generated gradients in vivo. Here we define the in vivo dynamics of one key guidance molecule, the chemokine Cxcl12a, by applying a fluorescent timer approach to measure ligand-triggered receptor turnover in living animals. Using the zebrafish lateral line primordium as a model, we show that migrating cell collectives can self-generate gradients of chemokine activity across their length via polarized receptor-mediated internalization. Finally, by engineering an external source of the atypical receptor Cxcr7 that moves with the primordium, we show that a self-generated gradient mechanism is sufficient to direct robust collective migration. This study thus provides, to our knowledge, the first in vivo proof for self-directed tissue migration through local shaping of an extracellular cue and provides a framework for investigating self-directed migration in many other contexts including cancer invasion.

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