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Dok4 is involved in Schwann cell myelination and axonal interaction in vitro
Author(s) -
Blugeon Corinne,
Le Crom Stéphane,
Richard Laurence,
Vallat JeanMichel,
Charnay Patrick,
Decker Laurence
Publication year - 2011
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.21106
Subject(s) - schwann cell , biology , axon , microbiology and biotechnology , neuroscience , signal transduction
The initial interaction between the Schwann cell and the axon is a complex and poorly understood aspect of the myelination process. To investigate the molecular mechanisms involved in this interaction and to identify novel genes required for myelination, we performed an RNA profiling analysis, comparing Schwann cells cultured alone or in the presence of neurons. This led to the selection of 30 genes, mostly upregulated on Schwann cell–axon interaction. Most of the identified proteins are associated with the extracellular space or signal transduction systems, consistent with possible roles in Schwann cell–axon interaction. We performed a functional analysis of one of these genes, Dok4 (downstream of kinase‐4), which encodes a membrane‐associated tyrosine kinase substrate. Silencing RNA‐mediated knock‐down of Dok4 severely affected in vitro myelination. Moreover, Dok4 is required at early stages in the myelination process, including the initial interaction with the axon, and is also involved in Schwann cell migration and proliferation. Finally, this analysis establishes the interest of our gene collection in further understanding of the molecular mechanisms involved in Schwann cell–axon interaction. © 2010 Wiley‐Liss, Inc.