Precise SDF1-mediated cell guidance is achieved through ligand clearance and microRNA-mediated decay

Author:

Lewellis Stephen W.1,Nagelberg Danielle1,Subedi Abhi1,Staton Alison2,LeBlanc Michelle1,Giraldez Antonio2,Knaut Holger1

Affiliation:

1. Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016

2. Department of Genetics, Yale University School of Medicine, New Haven, CT 06510

Abstract

During animal development, SDF1 simultaneously guides various cell types to different targets. As many targets are in close proximity to one another, it is unclear how the system avoids mistargeting. Zebrafish trigeminal sensory neurons express the SDF1 receptor Cxcr4b and encounter multiple SDF1 sources during migration, but ignore all but the correct one. We show that miR-430 and Cxcr7b regulation of SDF1a are required for precise guidance. In the absence of miR-430 or Cxcr7b, neurons responded to ectopic SDF1a sources along their route and did not reach their target. This was due to a failure to clear SDF1a transcript and protein from sites of expression that the migrating neurons had already passed. Our findings suggest an “attractive path” model in which migrating cells closely follow a dynamic SDF1a source that is refined on a transcript and protein level by miR-430 and Cxcr7b, respectively.

Publisher

Rockefeller University Press

Subject

Cell Biology

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