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, 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.
Câmara
Joana
J
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, England, UK.
Wang
Zhen
Z
Nunes-Fonseca
Cristina
C
Friedman
Hana C
HC
Grove
Matthew
M
Sherman
Diane L
DL
Komiyama
Noboru H
NH
Grant
Seth G
SG
Brophy
Peter J
PJ
Peterson
Alan
A
ffrench-Constant
Charles
C
D000818:Animals; D001369:Axons; D002450:Cell Communication; D002490:Central Nervous System / Q000166:cytology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D019012:Integrin beta1 / Q000502:physiology*; D039661:Integrin beta3 / Q000502:physiology; D016023:Integrins / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath; D009836:Oligodendroglia / Q000648:ultrastructure*
D019012:Integrin beta1; D039661:Integrin beta3; D016023:Integrins; D007041:Hypoxanthine Phosphoribosyltransferase