Publication Date:
2013-09-27
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dona, Erika -- Barry, Joseph D -- Valentin, Guillaume -- Quirin, Charlotte -- Khmelinskii, Anton -- Kunze, Andreas -- Durdu, Sevi -- Newton, Lionel R -- Fernandez-Minan, Ana -- Huber, Wolfgang -- Knop, Michael -- Gilmour, Darren -- England -- Nature. 2013 Nov 14;503(7475):285-9. doi: 10.1038/nature12635. Epub 2013 Sep 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉EMBL Heidelberg, Meyerhofstrasse 1, 69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24067609" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Movement/*physiology
;
Chemokine CXCL12/genetics/metabolism
;
Chemotactic Factors/genetics/*metabolism
;
Embryo, Nonmammalian
;
Gene Expression Regulation, Developmental
;
Receptors, CXCR/genetics/metabolism
;
Zebrafish/genetics/*physiology
;
Zebrafish Proteins/genetics/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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