title: Neuron-Specific Deletion of the Nf2 Tumor Suppressor Impairs Functional Nerve Regeneration.
abstract: In contrast to axons of the central nervous system (CNS), axons of the peripheral nervous system (PNS) show better, but still incomplete and often slow regeneration following injury. The tumor suppressor protein merlin, mutated in the hereditary tumor syndrome Neurofibromatosis type 2 (NF2), has recently been shown to have RhoA regulatory functions in PNS neurons-in addition to its well-characterized, growth-inhibitory activity in Schwann cells. Here we report that the conditional knockout of merlin in PNS neurons leads to impaired functional recovery of mice following sciatic nerve crush injury, in a gene-dosage dependent manner. Gross anatomical or electrophysiological alterations of sciatic nerves could not be detected. However, correlating with attenuated RhoA activation due to merlin deletion, ultrastructural analysis of nerve samples indicated enhanced sprouting of axons with reduced caliber size and increased myelination compared to wildtype animals. We conclude that deletion of the tumor suppressor merlin in the neuronal compartment of peripheral nerves results in compromised functional regeneration after injury. This mechanism could explain the clinical observation that NF2 patients suffer from higher incidences of slowly recovering facial nerve paralysis after vestibular schwannoma surgery.
authors.affiliation: Leibniz Institute on Aging, Fritz Lipmann Institute, 07745, Jena, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Leibniz Institute on Aging, Fritz Lipmann Institute, 07745, Jena, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Büttner
authors.affiliation: Institute of Anatomy, Anatomy and Cell Biology, University of Bonn, 53115, Bonn, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Toledo
authors.affiliation: Institute of Anatomy, Anatomy and Cell Biology, University of Bonn, 53115, Bonn, Germany.
authors.forename: Stephan L
authors.initials: SL
authors.lastname: Baader
authors.affiliation: Leibniz Institute on Aging, Fritz Lipmann Institute, 07745, Jena, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: von Maltzahn
authors.affiliation: Department of Otorhinolaryngology, Jena University Hospital, Friedrich Schiller University Jena, 07747, Jena, Germany.
authors.forename: Andrey
authors.initials: A
authors.lastname: Irintchev
authors.affiliation: Institute of Molecular Cell Biology & Center for Sepsis Control and Care (CSCC), Jena University Hospital, Friedrich Schiller University Jena, 07747, Jena, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bauer
authors.affiliation: Leibniz Institute on Aging, Fritz Lipmann Institute, 07745, Jena, Germany.
authors.forename: Helen
authors.initials: H
authors.lastname: Morrison
mesh_terms: D000818:Animals; D017353:Gene Deletion; D016515:Genes, Neurofibromatosis 2; D051379:Mice; D018345:Mice, Knockout; D009416:Nerve Regeneration / Q000502:physiology*