Directional tissue migration through a self-generated chemokine gradient
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...
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| Main Authors: | , , |
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| Format: | Article (Journal) Editorial |
| Language: | English |
| Published: |
25 September 2013
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| In: |
Nature
Year: 2013, Volume: 503, Issue: 7475, Pages: 285-289 |
| ISSN: | 1476-4687 |
| DOI: | 10.1038/nature12635 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/nature12635 Verlag, Volltext: https://www.nature.com/nature/journal/v503/n7475/full/nature12635.html 
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| Author Notes: | Erika Donà, Joseph D. Barry, Guillaume Valentin, Charlotte Quirin, Anton Khmelinskii, Andreas Kunze, Sevi Durdu, Lionel R. Newton, Ana Fernandez-Minan, Wolfgang Huber, Michael Knop & Darren Gilmour |
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| 245 | 1 | 0 | |a Directional tissue migration through a self-generated chemokine gradient |c Erika Donà, Joseph D. Barry, Guillaume Valentin, Charlotte Quirin, Anton Khmelinskii, Andreas Kunze, Sevi Durdu, Lionel R. Newton, Ana Fernandez-Minan, Wolfgang Huber, Michael Knop & Darren Gilmour |
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| 520 | |a 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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