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: https://orcid.org/0000-0002-5621-3377
(2009)
Integrin-mediated axoglial interactions initiate myelination in the central nervous system.
Journal of Cell Biology, 185 (4).
pp. 699-712.
ISSN 0021-9525
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.
Item Type: | Article |
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Uncontrolled Keywords: | cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1307 |
Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
Related URLs: | |
Depositing User: | LivePure Connector |
Date Deposited: | 16 Jul 2022 11:30 |
Last Modified: | 21 Jul 2024 01:20 |
URI: | https://ueaeprints.uea.ac.uk/id/eprint/86305 |
DOI: | 10.1083/jcb.200807010 |
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