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

TitleIntegrin-mediated axoglial interactions initiate myelination in the central nervous system.
Publication TypeJournal Article
Year of Publication2009
AuthorsCâmara J, Wang Z, Nunes-Fonseca C, Friedman HC, Grove M, Sherman DL, Komiyama NH, Grant SG, Brophy PJ, Peterson A, ffrench-Constant C
JournalJ Cell Biol
Date Published2009 May 18
KeywordsAnimals, Antigens, CD29, Axons, Cell Communication, Central Nervous System, Hypoxanthine Phosphoribosyltransferase, Integrin beta3, Integrins, Mice, Mice, Transgenic, Myelin Sheath, Oligodendroglia

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.

Alternate JournalJ. Cell Biol.
PubMed ID19451276
PubMed Central IDPMC2711572
Grant List669 / / Multiple Sclerosis Society / United Kingdom
G0601744 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom