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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Movement*
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Chemokine CXCL12 / genetics
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Chemokine CXCL12 / metabolism*
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Embryo, Nonmammalian / cytology
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Embryo, Nonmammalian / metabolism
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Gene Expression Regulation, Developmental
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Ligands
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MicroRNAs / metabolism*
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Models, Biological
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Mutation / genetics
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RNA Stability*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, CXCR / genetics
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Receptors, CXCR / metabolism*
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Receptors, CXCR4 / metabolism
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Signal Transduction / genetics
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Trigeminal Ganglion / cytology*
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Trigeminal Ganglion / metabolism*
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Zebrafish / embryology
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Zebrafish / genetics
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Zebrafish / metabolism*
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism*
Substances
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CXCR4b protein, zebrafish
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CXCR7 protein, zebrafish
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Chemokine CXCL12
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Ligands
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MicroRNAs
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Mirn430 microRNA, zebrafish
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RNA, Messenger
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Receptors, CXCR
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Receptors, CXCR4
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Zebrafish Proteins