title: Merlin controls the repair capacity of Schwann cells after injury by regulating Hippo/YAP activity.
abstract: Loss of the Merlin tumor suppressor and activation of the Hippo signaling pathway play major roles in the control of cell proliferation and tumorigenesis. We have identified completely novel roles for Merlin and the Hippo pathway effector Yes-associated protein (YAP) in the control of Schwann cell (SC) plasticity and peripheral nerve repair after injury. Injury to the peripheral nervous system (PNS) causes a dramatic shift in SC molecular phenotype and the generation of repair-competent SCs, which direct functional repair. We find that loss of Merlin in these cells causes a catastrophic failure of axonal regeneration and remyelination in the PNS. This effect is mediated by activation of YAP expression in Merlin-null SCs, and loss of YAP restores axonal regrowth and functional repair. This work identifies new mechanisms that control the regenerative potential of SCs and gives new insight into understanding the correct control of functional nerve repair in the PNS.
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth PL6 8BU, England, UK.
authors.forename: Thomas
authors.identifier: 0000-0003-0870-0696
authors.initials: T
authors.lastname: Mindos
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth PL6 8BU, England, UK.
authors.forename: Xin-Peng
authors.identifier: 0000-0003-2837-4672
authors.initials: XP
authors.lastname: Dun
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth PL6 8BU, England, UK.|University of Bath, Bath BA2 7AY, England, UK.
authors.forename: Katherine
authors.identifier: 0000-0002-7510-6614
authors.initials: K
authors.lastname: North
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth PL6 8BU, England, UK.
authors.forename: Robin D S
authors.initials: RD
authors.lastname: Doddrell
authors.affiliation: Leibniz Institute for Age Research - Fritz Lipmann Institute Jena, D-07745 Jena, Germany.
authors.forename: Alexander
authors.identifier: 0000-0003-1604-4596
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Department of Cellular and Anatomical Pathology, Derriford Hospital, Plymouth PL6 8DH, England, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Edwards
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth PL6 8BU, England, UK.
authors.forename: James
authors.identifier: 0000-0002-5241-741X
authors.initials: J
authors.lastname: Russell
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth PL6 8BU, England, UK.|University of Bath, Bath BA2 7AY, England, UK.
authors.forename: Bethany
authors.identifier: 0000-0003-0136-5485
authors.initials: B
authors.lastname: Gray
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth PL6 8BU, England, UK.
authors.forename: Sheridan L
authors.identifier: 0000-0002-7571-0598
authors.initials: SL
authors.lastname: Roberts
authors.affiliation: Department of Cellular and Anatomical Pathology, Derriford Hospital, Plymouth PL6 8DH, England, UK.
authors.forename: Aditya
authors.identifier: 0000-0003-2737-083X
authors.initials: A
authors.lastname: Shivane
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth PL6 8BU, England, UK.
authors.forename: Georgina
authors.identifier: 0000-0003-3759-399X
authors.initials: G
authors.lastname: Mortimer
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth PL6 8BU, England, UK.
authors.forename: Melissa
authors.identifier: 0000-0002-0923-4941
authors.initials: M
authors.lastname: Pirie
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Nailing
authors.identifier: 0000-0003-3612-215X
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Duojia
authors.identifier: 0000-0003-2890-4645
authors.initials: D
authors.lastname: Pan
authors.affiliation: Leibniz Institute for Age Research - Fritz Lipmann Institute Jena, D-07745 Jena, Germany.
authors.forename: Helen
authors.initials: H
authors.lastname: Morrison
authors.affiliation: Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth PL6 8BU, England, UK david.parkinson@plymouth.ac.uk.
authors.forename: David B
authors.identifier: 0000-0002-5704-4923
authors.initials: DB
authors.lastname: Parkinson
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D000071576:Crush Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D000090683:Hippo Signaling Pathway; D008297:Male; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009043:Motor Activity; D009186:Myelin Sheath / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009416:Nerve Regeneration; D025581:Neurofibromin 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity; D010641:Phenotype; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D020127:Recovery of Function; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction; D013997:Time Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D009414:Nerve Growth Factors; D025581:Neurofibromin 2; D010750:Phosphoproteins; D016755:Proto-Oncogene Proteins c-jun; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases