title: Ephrin-A3 promotes and maintains slow muscle fiber identity during postnatal development and reinnervation.
abstract: Each adult mammalian skeletal muscle has a unique complement of fast and slow myofibers, reflecting patterns established during development and reinforced via their innervation by fast and slow motor neurons. Existing data support a model of postnatal "matching" whereby predetermined myofiber type identity promotes pruning of inappropriate motor axons, but no molecular mechanism has yet been identified. We present evidence that fiber type-specific repulsive interactions inhibit innervation of slow myofibers by fast motor axons during both postnatal maturation of the neuromuscular junction and myofiber reinnervation after injury. The repulsive guidance ligand ephrin-A3 is expressed only on slow myofibers, whereas its candidate receptor, EphA8, localizes exclusively to fast motor endplates. Adult mice lacking ephrin-A3 have dramatically fewer slow myofibers in fast and mixed muscles, and misexpression of ephrin-A3 on fast myofibers followed by denervation/reinnervation promotes their respecification to a slow phenotype. We therefore conclude that Eph/ephrin interactions guide the fiber type specificity of neuromuscular interactions during development and adult life.
authors.affiliation: Division of Biological Sciences, University of Missouri, Columbia, MO 65211 Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211.
authors.forename: Danny A
authors.initials: DA
authors.lastname: Stark
authors.affiliation: Division of Biological Sciences, University of Missouri, Columbia, MO 65211.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Coffey
authors.affiliation: Division of Biological Sciences, University of Missouri, Columbia, MO 65211.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Pancoast
authors.affiliation: Division of Biological Sciences, University of Missouri, Columbia, MO 65211 Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Arnold
authors.affiliation: Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211.
authors.forename: J Peyton D
authors.initials: JP
authors.lastname: Walker
authors.affiliation: Département de Neurosciences, Université de Montréal, Montréal, Québec H3C 3J7, Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Vallée
authors.affiliation: Département de Neurosciences, Université de Montréal, Montréal, Québec H3C 3J7, Canada Groupe de Recherche sur le Système Nerveux Central, Université de Montréal, Montréal, Québec H3C 3J7, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Robitaille
authors.affiliation: Division of Biological Sciences, University of Missouri, Columbia, MO 65211 Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Garcia
authors.affiliation: Division of Biological Sciences, University of Missouri, Columbia, MO 65211 Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211 cornelisond@missouri.edu.
authors.forename: D D W
authors.initials: DD
authors.lastname: Cornelison
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009046:Motor Neurons / Q000502:physiology; D018482:Muscle, Skeletal / Q000196:embryology / Q000254:growth & development* / Q000294:innervation*; D009210:Myofibrils / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009469:Neuromuscular Junction / Q000502:physiology; D009473:Neuronal Plasticity; D010641:Phenotype; D036121:Receptor, EphA3 / Q000378:metabolism*; D036143:Receptor, EphA8 / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D012584:Sciatic Nerve / Q000502:physiology
chemical_list: D008024:Ligands; C491717:Epha3 protein, mouse; D036121:Receptor, EphA3; D036143:Receptor, EphA8