Integrin-mediated axoglial interactions initiate myelination in the central nervous system

Joana Câmara, Zhen Wang, Cristina Nunes-Fonseca, Hana C. Friedman, Matthew Grove, Diane L. Sherman, Noboru H. Komiyama, Seth G. Grant, Peter J. Brophy, Alan Peterson, Charles Ffrench-Constant

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66 Citations (Scopus)

Abstract

All but the smallest-diameter axons in the central nervous system are myelinated, but the signals that initiate myelination are unknown. Our prior work has shown that integrin signaling forms part of the cell-cell interactions that ensure only those oligodendrocytes contacting axons survive. Here, therefore, we have asked whether integrins regulate the interactions that lead to myelination. Using homologous recombination to insert a single-copy transgene into the hypoxanthine phosphoribosyl transferase (hprt) locus, we find that mice expressing a dominant-negative β1 integrin in myelinating oligodendrocytes require a larger axon diameter to initiate timely myelination. Mice with a conditional deletion of focal adhesion kinase (a signaling molecule activated by integrins) exhibit a similar phenotype. Conversely, transgenic mice expressing dominant-negative β3 integrin in oligodendrocytes display no myelination abnormalities. We conclude that β1 integrin plays a key role in the axoglial interactions that sense axon size and initiate myelination, such that loss of integrin signaling leads to a delay in myelination of small-diameter axons.

Original languageEnglish
Pages (from-to)699-712
Number of pages14
JournalJournal of Cell Biology
Volume185
Issue number4
DOIs
Publication statusPublished - 18 May 2009

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