Lewellis, S.W., Nagelberg, D., Subedi, A., Staton, A., Leblanc, M., Giraldez, A., and Knaut, H. (2013) Precise SDF1-mediated cell guidance is achieved through ligand clearance and microRNA-mediated decay. The Journal of cell biology. 200(3):337-355.
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.