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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
PubMed

Insights

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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