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Published on: August 27, 2015
Precise SDF1-mediated cell guidance is achieved through ligand clearance and microRNA-mediated decay
Stephen W Lewellis1, Danielle Nagelberg, Abhi Subedi
1Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.
The Journal of Cell Biology
|February 6, 2013
Summary
Precise cell guidance during development relies on regulating SDF1a. MicroRNA-430 (miR-430) and Cxcr7b ensure migrating neurons follow the correct path by clearing SDF1a signals.
Area of Science:
- Developmental biology
- Neuroscience
- Molecular biology
Background:
- Chemokine SDF1a guides multiple cell types during development.
- Proximity of targets raises questions about precise cell migration and avoiding mistargeting.
- Zebrafish trigeminal sensory neurons navigate complex SDF1a gradients.
Purpose of the Study:
- Investigate mechanisms ensuring precise neuronal migration in zebrafish.
- Determine the role of miR-430 and Cxcr7b in SDF1a-mediated guidance.
- Elucidate how neurons ignore incorrect SDF1a cues.
Main Methods:
- Studied zebrafish trigeminal sensory neuron migration.
- Assessed the function of miR-430 and Cxcr7b in SDF1a guidance.
- Analyzed SDF1a transcript and protein clearance.
Main Results:
- miR-430 and Cxcr7b are essential for accurate SDF1a guidance.
- Absence of miR-430 or Cxcr7b leads to mistargeting due to ectopic SDF1a response.
- Failure to clear SDF1a transcript/protein from passed sites caused navigation errors.
Conclusions:
- miR-430 and Cxcr7b regulate SDF1a for precise neuronal pathfinding.
- An "attractive path" model explains dynamic SDF1a source following.
- Transcript and protein clearance are critical for developmental cell migration accuracy.
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