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

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, t...

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Autores principales: 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, ffrench-Constant, Charles
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711572/
https://www.ncbi.nlm.nih.gov/pubmed/19451276
http://dx.doi.org/10.1083/jcb.200807010
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author 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
ffrench-Constant, Charles
author_facet 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
ffrench-Constant, Charles
author_sort Câmara, Joana
collection PubMed
description 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.
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spelling pubmed-27115722009-11-18 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 ffrench-Constant, Charles J Cell Biol Research Articles 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. The Rockefeller University Press 2009-05-18 /pmc/articles/PMC2711572/ /pubmed/19451276 http://dx.doi.org/10.1083/jcb.200807010 Text en © 2009 Câmara et al. 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/).
spellingShingle Research Articles
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
ffrench-Constant, Charles
Integrin-mediated axoglial interactions initiate myelination in the central nervous system
title Integrin-mediated axoglial interactions initiate myelination in the central nervous system
title_full Integrin-mediated axoglial interactions initiate myelination in the central nervous system
title_fullStr Integrin-mediated axoglial interactions initiate myelination in the central nervous system
title_full_unstemmed Integrin-mediated axoglial interactions initiate myelination in the central nervous system
title_short Integrin-mediated axoglial interactions initiate myelination in the central nervous system
title_sort integrin-mediated axoglial interactions initiate myelination in the central nervous system
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711572/
https://www.ncbi.nlm.nih.gov/pubmed/19451276
http://dx.doi.org/10.1083/jcb.200807010
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