Inhibition of N-cadherin and β-catenin function reduces axon-induced schwann cell proliferation

Burkhard Gess, Hartmut Halfter, Ilka Kleffner, Paula Monje, Gagani Athauda, Patrick M. Wood, Peter Young, Ina B. Wanner

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

N-cadherin and β-catenin are involved in cell adhesion and cell cycle in tumor cells and neural crest. Both are expressed at key stages of Schwann cell (SC) development, but little is known about their function in the SC lineage. We studied the role of these molecules in adult rat derived SC-embryonic dorsal root ganglion cocultures by using low-Ca2+ conditions and specific blocking antibodies to interfere with N-cadherin function and by using small interfering RNA (siRNA) to decrease β-catenin expression in both SC-neuron cocultures and adult rat-derived SC monocultures. N-cadherin blocking conditions decreased SC-axon association and reduced axon-induced SC proliferation. In SC monocultures, β-catenin reduction diminished the proliferative response of SCs to the mitogen β1-heregulin, and, in SC-DRG cocultures, β-catenin reduction inhibited axon-contact-dependent SC proliferation. Stimulation of SC cultures with β1-heregulin increased total β-catenin protein amount, phosphorylation of GSK-3β and β-catenin presence in nuclear extracts. In conclusion, our findings suggest a previously unrecognized contribution of β-catenin and N-cadherin to axon-induced SC proliferation.

Original languageEnglish (US)
Pages (from-to)797-812
Number of pages16
JournalJournal of Neuroscience Research
Volume86
Issue number4
DOIs
StatePublished - Mar 1 2008

Keywords

  • β-catenin
  • DRG
  • N-cadherin
  • Proliferation
  • RNAi
  • Schwann cell

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Gess, B., Halfter, H., Kleffner, I., Monje, P., Athauda, G., Wood, P. M., Young, P., & Wanner, I. B. (2008). Inhibition of N-cadherin and β-catenin function reduces axon-induced schwann cell proliferation. Journal of Neuroscience Research, 86(4), 797-812. https://doi.org/10.1002/jnr.21528