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

Joana Câmara, Zhen Wang, Cristina Nunes-Fonseca, Hana C Friedman, Matthew Grove, Diane L Sherman, Noboru H Komiyama, Seth G Grant, Peter J Brophy, Alan Peterson, Charles ffrench-Constant

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)699-712
Number of pages14
JournalJournal of Cell Biology
Issue number4
Publication statusPublished - May 2009


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


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