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- Title
α2-Chimaerin Is Required for Eph Receptor-Class-Specific Spinal Motor Axon Guidance and Coordinate Activation of Antagonistic Muscles.
- Authors
Tzu-Jen Kao; Nicholl, Georgina C. B.; Johansen, Jamie A.; Kania, Artur; Beg, Asim A.
- Abstract
Axonal guidance involves extrinsic molecular cues that bind growth cone receptors and signal to the cytoskeleton through divergent pathways. Some signaling intermediates are deployed downstream of molecularly distinct axon guidance receptor families, but the scope of this overlap is unclear, as is the impact of embryonic axon guidance fidelity on adult nervous system function. Here, we demonstrate that the Rho-GTPase-activating protein α2-chimaerin is specifically required for EphA and not EphB receptor signaling in mouse and chick spinal motor axons. Reflecting this specificity, the loss of α2-chimaerin function disrupts the limb trajectory of extensor-muscle innervating motor axons the guidance of which depends on EphA signaling. These embryonic defects affect coordinated contraction of antagonistic flexor-extensor muscles in the adult, indicating that accurate embryonic motor axon guidance is critical for optimal neuromuscular function. Together, our observations provide the first functional evidence of an Eph receptor-class-specific intracellular signaling protein that is required for appropriate neuromuscular connectivity.
- Subjects
CELLULAR signal transduction; EPHRIN receptors; REGULATION of muscle contraction; MOTOR neurons; CHIMERISM; GTPASE-activating protein; RECEPTOR-ligand complexes; GENE expression
- Publication
Journal of Neuroscience, 2015, Vol 35, Issue 6, p2344
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.4151-14.2015