title: The small GTPase RhoA is required for proper locomotor circuit assembly.
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.
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Shalaka
authors.initials: S
authors.lastname: Mulherkar
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Qin
authors.initials: Q
authors.lastname: Chen
authors.forename: Anjana
authors.initials: A
authors.lastname: Narayanan
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Couvillon
authors.forename: H David
authors.initials: HD
authors.lastname: Shine
authors.forename: Kimberley F
authors.initials: KF
authors.lastname: Tolias
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000166:cytology; D036389:Ephrin-B3 / Q000378:metabolism; D055786:Gene Knockout Techniques; D020439:Growth Cones / Q000378:metabolism; D008124:Locomotion; D051379:Mice; D008969:Molecular Sequence Data; D009415:Nerve Net / Q000166:cytology / Q000201:enzymology* / Q000502:physiology*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D036122:Receptor, EphA4 / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology; D020742:rhoA GTP-Binding Protein / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D036389:Ephrin-B3; D036122:Receptor, EphA4; D020742:rhoA GTP-Binding Protein