title: Nf2/Merlin controls spinal cord neural progenitor function in a Rac1/ErbB2-dependent manner.
abstract: OBJECTIVE
  Individuals with the neurofibromatosis type 2 (NF2) cancer predisposition syndrome develop spinal cord glial tumors (ependymomas) that likely originate from neural progenitor cells. Whereas many spinal ependymomas exhibit indolent behavior, the only treatment option for clinically symptomatic tumors is surgery. In this regard, medical therapies are unfortunately lacking due to an incomplete understanding of the critical growth control pathways that govern the function of spinal cord (SC) neural progenitor cells (NPCs).
  
  
  METHODS
  To identify potential therapeutic targets for these tumors, we leveraged primary mouse Nf2-deficient spinal cord neural progenitor cells.
  
  
  RESULTS
  We demonstrate that the Nf2 protein, merlin, negatively regulates spinal neural progenitor cell survival and glial differentiation in an ErbB2-dependent manner, and that NF2-associated spinal ependymomas exhibit increased ErbB2 activation. Moreover, we show that Nf2-deficient SC NPC ErbB2 activation results from Rac1-mediated ErbB2 retention at the plasma membrane.
  
  
  CONCLUSIONS
  Collectively, these findings establish ErbB2 as a potential rational therapeutic target for NF2-associated spinal ependymoma.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Garcia
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: David H
authors.initials: DH
authors.lastname: Gutmann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D004806:Ependymoma / Q000188:drug therapy / Q000503:physiopathology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology*; D025581:Neurofibromin 2 / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013120:Spinal Cord Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D025581:Neurofibromin 2; D009479:Neuropeptides; D018719:Erb-b2 Receptor Tyrosine Kinases; D020830:rac1 GTP-Binding Protein; C484602:Rac1 protein, mouse; C524056:Erbb2 protein, mouse