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

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    Rights statement: This article is distributed under the terms of an Attribution– Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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http://jcb.rupress.org/content/185/4/699
Original languageEnglish
Pages (from-to)699-712
Number of pages14
JournalThe Journal of Cell Biology
Volume185
Issue number4
DOIs
Publication statusPublished - May 2009

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 beta1 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 beta3 integrin in oligodendrocytes display no myelination abnormalities. We conclude that beta1 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.

    Research areas

  • Animals, Antigens, CD29, Axons, Cell Communication, Central Nervous System, Hypoxanthine Phosphoribosyltransferase, Integrin beta3, Integrins, Mice, Myelin Sheath, Oligodendroglia, Transgenic

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