Directional tissue migration through a self-generated chemokine gradient
- Authors
- 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.
- ID
- ZDB-PUB-131024-18
- 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
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.