title: Precise SDF1-mediated cell guidance is achieved through ligand clearance and microRNA-mediated decay.
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.
authors: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors: Stephen W
authors: SW
authors: Lewellis
authors: Danielle
authors: D
authors: Nagelberg
authors: Abhi
authors: A
authors: Subedi
authors: Alison
authors: A
authors: Staton
authors: Michelle
authors: M
authors: LeBlanc
authors: Antonio
authors: A
authors: Giraldez
authors: Holger
authors: H
authors: Knaut
mesh_terms: D000818:Animals; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008024:Ligands; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012668:Trigeminal Ganglion / Q000166:cytology* / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C471276:CXCR4b protein, zebrafish; C519524:CXCR7 protein, zebrafish; D054377:Chemokine CXCL12; D008024:Ligands; D035683:MicroRNAs; C557527:Mirn430 microRNA, zebrafish; D012333:RNA, Messenger; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D029961:Zebrafish Proteins
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