title: α2-chimaerin is required for Eph receptor-class-specific spinal motor axon guidance and coordinate activation of antagonistic muscles.
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.
authors: Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7 Canada, Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology and Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei, Taiwan, and.
authors: Tzu-Jen
authors: TJ
authors: Kao
authors: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors: Georgina C B
authors: http://orcid.org/0000-0003-4742-2342
authors: GC
authors: Nicholl
authors: College of Medicine, Central Michigan University, Mount Pleasant, Michigan 48859.
authors: Jamie A
authors: JA
authors: Johansen
authors: Institut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7 Canada, Departments of Anatomy and Cell Biology and Biology, Division of Experimental Medicine, McGill University Montréal, Quebec H3A 2B2, Canada, and Faculté de Médecine, Université de Montréal, Montréal, Quebec H3C 3J7, Canada, asimbeg@umich.edu artur.kania@ircm.qc.ca.
authors: Artur
authors: A
authors: Kania
authors: Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109, Neuroscience Program, University of Michigan, Ann Arbor MI 48109, asimbeg@umich.edu artur.kania@ircm.qc.ca.
authors: Asim A
authors: AA
authors: Beg
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002642:Chick Embryo; D020848:Chimerin 1 / Q000235:genetics* / Q000502:physiology*; D005684:Gait / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation* / Q000502:physiology*; D004856:Postural Balance / Q000502:physiology; D036081:Receptors, Eph Family / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D020848:Chimerin 1; D036081:Receptors, Eph Family; D020741:rho GTP-Binding Proteins
keywords: axon guidance; chimaerin; motor neurons; muscle contraction