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Inhibition of N‐cadherin and β‐catenin function reduces axon‐induced Schwann cell proliferation
Author(s) -
Gess Burkhard,
Halfter Hartmut,
Kleffner Ilka,
Monje Paula,
Athauda Gagani,
Wood Patrick M.,
Young Peter,
Wanner Ina B.
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21528
Subject(s) - cadherin , microbiology and biotechnology , catenin , axon , biology , neuregulin , neural crest , schwann cell , dorsal root ganglion , cell , signal transduction , neuroscience , embryo , spinal cord , biochemistry , wnt signaling pathway
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‐Ca 2+ 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. © 2007 Wiley‐Liss, Inc.