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Dok4 is involved in Schwann cell myelination and axonal interaction in vitro

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.