The small GTPase RhoA is required for proper locomotor circuit assembly

PLoS One. 2013 Jun 25;8(6):e67015. doi: 10.1371/journal.pone.0067015. Print 2013.

Abstract

The assembly of neuronal circuits during development requires the precise navigation of axons, which is controlled by attractive and repulsive guidance cues. In the developing spinal cord, ephrinB3 functions as a short-range repulsive cue that prevents EphA4 receptor-expressing corticospinal tract and spinal interneuron axons from crossing the midline, ensuring proper formation of locomotor circuits. Here we report that the small GTPase RhoA, a key regulator of cytoskeletal dynamics, is also required for ephrinB3/EphA4-dependent locomotor circuit formation. Deletion of RhoA from neural progenitor cells results in mice that exhibit a rabbit-like hopping gait, which phenocopies mice lacking ephrinB3 or EphA4. Consistent with this locomotor defect, we found that corticospinal tract axons and spinal interneuron projections from RhoA-deficient mice aberrantly cross the spinal cord midline. Furthermore, we determined that loss of RhoA blocks ephrinB3-induced growth cone collapse of cortical axons and disrupts ephrinB3 expression at the spinal cord midline. Collectively, our results demonstrate that RhoA is essential for the ephrinB3/EphA4-dependent assembly of cortical and spinal motor circuits that control normal locomotor behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / cytology
  • Ephrin-B3 / metabolism
  • Gene Knockout Techniques
  • Growth Cones / metabolism
  • Locomotion*
  • Mice
  • Molecular Sequence Data
  • Nerve Net / cytology
  • Nerve Net / enzymology*
  • Nerve Net / physiology*
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Receptor, EphA4 / metabolism
  • Spinal Cord / cytology
  • rhoA GTP-Binding Protein / chemistry
  • rhoA GTP-Binding Protein / deficiency
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism*

Substances

  • Ephrin-B3
  • Receptor, EphA4
  • rhoA GTP-Binding Protein

Grant support

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.