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Assaying the Ability of Diffusible Signaling Molecules to Reorient Embryonic Spinal Commissural Axons
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RabGDI controls axonal midline crossing by regulating Robo1 surface expression.

Melanie Philipp1, Vera Niederkofler, Marc Debrunner

  • 1Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, Zurich, CH 8057, Switzerland.

Neural Development
|November 13, 2012
PubMed
Summary

RabGDI regulates Robo1 surface expression, enabling commissural axons to switch from attraction to repulsion at choice points. This is crucial for axon guidance during nervous system development.

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Molecular Biology

Background:

  • Axon guidance relies on intermediate targets expressing guidance cues.
  • Axons must switch responsiveness from attraction to repulsion at choice points.
  • Mechanisms for this responsiveness switch in commissural axons are unclear.

Purpose of the Study:

  • To investigate the role of RabGDI in commissural axon guidance.
  • To understand how RabGDI influences axon responsiveness at choice points.

Main Methods:

  • Differential gene expression screening identified RabGDI in floor-plate genes.
  • In ovo RNA interference (RNAi) was used to downregulate RabGDI.
  • Axon behavior was observed in vivo and in cultured neurons.

Main Results:

  • RabGDI downregulation caused commissural axons to stall in the floor plate, similar to Robo1 downregulation.
  • Premature RabGDI expression blocked commissural axon entry into the floor plate.
  • RabGDI induced Robo1 surface expression in cultured commissural neurons.

Conclusions:

  • RabGDI regulates Robo1 surface expression, functionally replacing Drosophila's Commissureless (Comm) in vertebrates.
  • This regulation enables commissural axons to switch from attraction to repulsion at the spinal cord midline.
  • RabGDI is identified as a key component in the mechanism for switching axon responsiveness at intermediate targets.