| First Author | Mulherkar S | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 6 | Pages | e67015 |
| PubMed ID | 23825607 | Mgi Jnum | J:203741 |
| Mgi Id | MGI:5528613 | Doi | 10.1371/journal.pone.0067015 |
| Citation | Mulherkar S, et al. (2013) The small GTPase RhoA is required for proper locomotor circuit assembly. PLoS One 8(6):e67015 |
| abstractText | 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. |
