title: Neuregulin1 displayed on motor axons regulates terminal Schwann cell-mediated synapse elimination at developing neuromuscular junctions.
abstract: Synaptic connections in the nervous system are rearranged during development and in adulthood as a feature of growth, plasticity, aging, and disease. Glia are implicated as active participants in these changes. Here we investigated a signal that controls the participation of peripheral glia, the terminal Schwann cells (SCs), at the neuromuscular junction (NMJ) in mice. Transgenic manipulation of the levels of membrane-tethered neuregulin1 (NRG1-III), a potent activator of SCs normally presented on motor axons, alters the rate of loss of motor inputs at NMJs during developmental synapse elimination. In addition, NMJs of adult transgenic mice that expressed excess axonal NRG1-III exhibited continued remodeling, in contrast to the more stable morphologies of controls. In fact, synaptic SCs of these adult mice with NRG1-III overexpression exhibited behaviors evident in wild type neonates during synapse elimination, including an affinity for the postsynaptic myofiber surface and phagocytosis of nerve terminals. Given that levels of NRG1-III expression normally peak during the period of synapse elimination, our findings identify axon-tethered NRG1 as a molecular determinant for SC-driven neuromuscular synaptic plasticity.
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX 77843; wiley@tamu.edu wthompson@bio.tamu.edu.
authors.forename: Young Il
authors.identifier: http://orcid.org/0000-0003-4993-9038
authors.initials: YI
authors.lastname: Lee
authors.affiliation: Dell Pediatric Research Institute, The University of Texas, Austin, TX 78712;
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Section of Molecular Cell and Developmental Biology, The University of Texas, Austin, TX 78712;
authors.forename: Michelle
authors.initials: M
authors.lastname: Mikesh
authors.affiliation: Institute for Neuroscience, Texas A&M University, College Station, TX 77843;
authors.forename: Ian
authors.initials: I
authors.lastname: Smith
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany;
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
authors.affiliation: Department of Cellular Neurophysiology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Markus H
authors.initials: MH
authors.lastname: Schwab
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX 77843; wiley@tamu.edu wthompson@bio.tamu.edu.
authors.forename: Wesley J
authors.initials: WJ
authors.lastname: Thompson
mesh_terms: D017398:Alternative Splicing; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D001369:Axons / Q000737:chemistry / Q000502:physiology; D018628:Gene Dosage; D006579:Heterozygote; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000737:chemistry / Q000502:physiology*; D018482:Muscle, Skeletal / Q000254:growth & development / Q000294:innervation; D009334:Neck Muscles / Q000254:growth & development / Q000294:innervation; D020890:Neuregulin-1 / Q000235:genetics / Q000502:physiology*; D009469:Neuromuscular Junction / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure*; D009473:Neuronal Plasticity / Q000502:physiology*; D010587:Phagocytosis / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011950:Receptors, Cholinergic / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000502:physiology*; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D008565:Membrane Proteins; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D020033:Protein Isoforms; D011950:Receptors, Cholinergic; D011993:Recombinant Fusion Proteins; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse
keywords: Schwann cell; neuregulin1; neuromuscular junction; synapse elimination; synaptic competition