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Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo

Jorgensen, Jesper Roland; Fransson, Anette; Fjord-Larsen, Lone; Thompson, Lachlan H.; Houchins, Jeffrey P.; Andrade, Nuno LU ; Torp, Malene; Kalkkinen, Nisse; Andersson, Elisabet and Lindvall, Olle LU , et al. (2012) In Experimental Neurology 233(1). p.172-181
Abstract
Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved protein family. During early mouse development, Cometin is found exclusively in the floor plate and from E13.5 also in dorsal root ganglions and inner ear but apparently not in the adult nervous system. In vitro, Cometin promotes neurite outgrowth from dorsal root ganglion cells which can be blocked by inhibition of the Janus or MEK kinases. In this assay, additive effects of Cometin and Meteorin are observed indicating separate receptors.... (More)
Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved protein family. During early mouse development, Cometin is found exclusively in the floor plate and from E13.5 also in dorsal root ganglions and inner ear but apparently not in the adult nervous system. In vitro, Cometin promotes neurite outgrowth from dorsal root ganglion cells which can be blocked by inhibition of the Janus or MEK kinases. In this assay, additive effects of Cometin and Meteorin are observed indicating separate receptors. Furthermore, Cometin supports migration of neuroblasts from subventricular zone explants to the same extend as stromal cell derived factor la. Given the neurotrophic properties in vitro, combined with the restricted inner ear expression during development, we further investigated Cometin in relation to deafness. In neomycin deafened guinea pigs, two weeks intracochlear infusion of recombinant Cometin supports spiral ganglion neuron survival and function. In contrast to the control group receiving artificial perilymph, Cometin treated animals retain normal electrically-evoked brainstem response which is maintained several weeks after treatment cessation. Neuroprotection is also evident from stereological analysis of the spiral ganglion. Altogether, these studies show that Cometin is a potent new neurotrophic factor with therapeutic potential. (C) 2011 Elsevier Inc. All rights reserved. (Less)
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keywords
Floor plate, Meteorin, Migration, Neurotrophic, Trophic factor, Spiral, ganglion, Novel protein
in
Experimental Neurology
volume
233
issue
1
pages
172 - 181
publisher
Academic Press
external identifiers
  • wos:000300123900021
  • scopus:84856214544
ISSN
0014-4886
DOI
10.1016/j.expneurol.2011.09.027
language
English
LU publication?
yes
id
95fa3f61-ba17-4e4e-9f35-ee024214f74f (old id 2390661)
date added to LUP
2012-04-02 09:24:12
date last changed
2017-06-11 03:19:46
@article{95fa3f61-ba17-4e4e-9f35-ee024214f74f,
  abstract     = {Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved protein family. During early mouse development, Cometin is found exclusively in the floor plate and from E13.5 also in dorsal root ganglions and inner ear but apparently not in the adult nervous system. In vitro, Cometin promotes neurite outgrowth from dorsal root ganglion cells which can be blocked by inhibition of the Janus or MEK kinases. In this assay, additive effects of Cometin and Meteorin are observed indicating separate receptors. Furthermore, Cometin supports migration of neuroblasts from subventricular zone explants to the same extend as stromal cell derived factor la. Given the neurotrophic properties in vitro, combined with the restricted inner ear expression during development, we further investigated Cometin in relation to deafness. In neomycin deafened guinea pigs, two weeks intracochlear infusion of recombinant Cometin supports spiral ganglion neuron survival and function. In contrast to the control group receiving artificial perilymph, Cometin treated animals retain normal electrically-evoked brainstem response which is maintained several weeks after treatment cessation. Neuroprotection is also evident from stereological analysis of the spiral ganglion. Altogether, these studies show that Cometin is a potent new neurotrophic factor with therapeutic potential. (C) 2011 Elsevier Inc. All rights reserved.},
  author       = {Jorgensen, Jesper Roland and Fransson, Anette and Fjord-Larsen, Lone and Thompson, Lachlan H. and Houchins, Jeffrey P. and Andrade, Nuno and Torp, Malene and Kalkkinen, Nisse and Andersson, Elisabet and Lindvall, Olle and Ulfendahl, Mats and Brunak, Soren and Johansen, Teit E. and Wahlberg, Lars U.},
  issn         = {0014-4886},
  keyword      = {Floor plate,Meteorin,Migration,Neurotrophic,Trophic factor,Spiral,ganglion,Novel protein},
  language     = {eng},
  number       = {1},
  pages        = {172--181},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2011.09.027},
  volume       = {233},
  year         = {2012},
}