NGF regulates the expression of axonal LINGO-1 to inhibit oligodendrocyte differentiation and myelination

Xinhua Lee, Zhongshu Yang, Zhaohui Shao, Sheila S. Rosenberg, Melissa Levesque, R. Blake Pepinsky, Mengsheng Qiu, Robert H. Miller, Jonah R. Chan, Sha Mi

Research output: Contribution to journalArticle

129 Scopus citations

Abstract

Neurons and glia share a mutual dependence in establishing a functional relationship, and none is more evident than the process by which axons control myelination. Here, we identify LRR and Ig domain-containing, Nogo receptor-interacting protein (LINGO-1) as a potent axonal inhibitor of oligodendrocyte differentiation and myelination that is regulated by nerve growth factor and its cognate receptor TrkA in a dose-dependent manner. Whereas LINGO-1 expressed by oligodendrocyte progenitor cells was previously identified as an inhibitor of differentiation, we demonstrate that axonal expression of LINGO-1 inhibits differentiation with equal potency. Disruption of LINGO-1 on either cell type is sufficient to overcome the inhibitory action and promote differentiation and myelination, independent of axon diameter. Furthermore, these results were recapitulated in transgenic mice overexpressing the full length LINGO-1 under the neuronal promoter synapsin. Myelination was greatly inhibited in the presence of enforced axonal LINGO-1. The implications of these results relate specifically to the development of potential therapeutics targeting extrinsic growth factors that may regulate the axonal expression of modulators of oligodendrocyte development.

Original languageEnglish (US)
Pages (from-to)220-225
Number of pages6
JournalJournal of Neuroscience
Volume27
Issue number1
DOIs
StatePublished - Jan 3 2007
Externally publishedYes

Keywords

  • Differentation
  • Dorsal root ganglion
  • LINGO-1
  • Myelination
  • Neurotrophin
  • Oligodendrocyte

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Lee, X., Yang, Z., Shao, Z., Rosenberg, S. S., Levesque, M., Pepinsky, R. B., Qiu, M., Miller, R. H., Chan, J. R., & Mi, S. (2007). NGF regulates the expression of axonal LINGO-1 to inhibit oligodendrocyte differentiation and myelination. Journal of Neuroscience, 27(1), 220-225. https://doi.org/10.1523/JNEUROSCI.4175-06.2007