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

Câmara, Joana, Wang, Zhen, Nunes-Fonseca, Cristina, Friedman, Hana C., Grove, Matthew, Sherman, Diane L., Komiyama, Noboru H., Grant, Seth G., Brophy, Peter J., Peterson, Alan and Ffrench-Constant, Charles ORCID: (2009) Integrin-mediated axoglial interactions initiate myelination in the central nervous system. Journal of Cell Biology, 185 (4). pp. 699-712. ISSN 0021-9525

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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.

Item Type: Article
Uncontrolled Keywords: cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1307
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 16 Jul 2022 11:30
Last Modified: 22 Oct 2022 18:37
DOI: 10.1083/jcb.200807010

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