title: Mammalian Nkx2.2+ perineurial glia are essential for motor nerve development.
abstract: BACKGROUND
  All vertebrate peripheral nerves connect the central nervous system (CNS) with targets in the periphery and are composed of axons, layers of ensheathing glia and connective tissue. Although the structure of these conduits is well established, very little is known about the origin and developmental roles of some of their elements. One understudied component, the perineurium, ensheaths nerve fascicles and is a component of the blood-nerve-barrier. In zebrafish, the motor nerve perineurium is composed of CNS-derived nkx2.2a(+) perineurial glia, which establish the motor exit point (MEP) during development. To determine if mouse perineurial cells also originate within the CNS and perform a similar function, we created a Nkx2.2:EGFP transgenic reporter line.
  
  
  RESULTS
  In conjunction with RNA expression analysis and antibody labeling, we observed Nkx2.2(+) cells along peripheral motor nerves at all stages of development and in adult tissue. Additionally, in mice lacking Nkx2.2, we demonstrate that Nkx2.2(+) perineurial glia are essential for motor nerve development and Schwann cell differentiation.
  
  
  CONCLUSIONS
  Our studies reveal that a subset of mouse perineurial cells are CNS-derived, express Nkx2.2, and are essential for motor nerve development. This work highlights an under-appreciated but essential contribution of CNS-derived cells to the development of the mammalian peripheral nervous system (PNS).
authors: Department of Biology, University of Virginia, Charlottesville, Virginia.
authors: Jessica K
authors: JK
authors: Clark
authors: Ashley
authors: A
authors: O'keefe
authors: Teresa L
authors: TL
authors: Mastracci
authors: Lori
authors: L
authors: Sussel
authors: Michael P
authors: MP
authors: Matise
authors: Sarah
authors: S
authors: Kucenas
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D010525:Peripheral Nerves / Q000166:cytology* / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D029961:Zebrafish Proteins
chemical_list: D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C000715627:Nkx2-2 protein, mouse; D014157:Transcription Factors; D029961:Zebrafish Proteins; C000715630:nkx2.2b protein, zebrafish
keywords: Schwann cell; motor nerve; perineurial glia; perineurium; peripheral nervous system; perisynaptic Schwann cell