title: Dynamic membrane depolarization is an early regulator of ependymoglial cell response to spinal cord injury in axolotl.
abstract: Salamanders, such as the Mexican axolotl, are some of the few vertebrates fortunate in their ability to regenerate diverse structures after injury. Unlike mammals they are able to regenerate a fully functional spinal cord after injury. However, the molecular circuitry required to initiate a pro-regenerative response after spinal cord injury is not well understood. To address this question we developed a spinal cord injury model in axolotls and used in vivo imaging of labeled ependymoglial cells to characterize the response of these cells to injury. Using in vivo imaging of ion sensitive dyes we identified that spinal cord injury induces a rapid and dynamic change in the resting membrane potential of ependymoglial cells. Prolonged depolarization of ependymoglial cells after injury inhibits ependymoglial cell proliferation and subsequent axon regeneration. Using transcriptional profiling we identified c-Fos as a key voltage sensitive early response gene that is expressed specifically in the ependymoglial cells after injury. This data establishes that dynamic changes in the membrane potential after injury are essential for regulating the specific spatiotemporal expression of c-Fos that is critical for promoting faithful spinal cord regeneration in axolotl.
authors.affiliation: Dept. of Genetics, Cell Biology and Development, University of Minnesota, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Sabin
authors.affiliation: CRTD/DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
authors.forename: Tiago
authors.initials: T
authors.lastname: Santos-Ferreira
authors.affiliation: Dept. of Genetics, Cell Biology and Development, University of Minnesota, USA.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Essig
authors.affiliation: Dept. of Genetics, Cell Biology and Development, University of Minnesota, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rudasill
authors.affiliation: Dept. of Genetics, Cell Biology and Development, University of Minnesota, USA. Electronic address: echev020@umn.edu.
authors.forename: Karen
authors.initials: K
authors.lastname: Echeverri
mesh_terms: D000558:Ambystoma mexicanum / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D063928:Ependymoglial Cells / Q000187:drug effects / Q000473:pathology*; D020869:Gene Expression Profiling; D005998:Glycine / Q000494:pharmacology; D007559:Ivermectin / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000503:physiopathology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D007559:Ivermectin; D005998:Glycine
keywords: Axolotl; Ependymoglial; Membrane potential; Regeneration