Beta1-integrin signaling mediates premyelinating oligodendrocyte survival but is not required for CNS myelination and remyelination.
Previous reports, including transplantation experiments using dominant-negative inhibition of beta1-integrin signaling in oligodendrocyte progenitor cells, suggested that beta1-integrin signaling is required for myelination. Here, we test this hypothesis using conditional ablation of the beta1-integrin gene in oligodendroglial cells during the development of the CNS. This approach allowed us to study oligodendroglial beta1-integrin signaling in the physiological environment of the CNS, circumventing the potential drawbacks of a dominant-negative approach. We found that beta1-integrin signaling has a much more limited role than previously expected. Although it was involved in stage-specific oligodendrocyte cell survival, beta1-integrin signaling was not required for axon ensheathment and myelination per se. We also found that, in the spinal cord, remyelination occurred normally in the absence of beta1-integrin. We conclude that, although beta1-integrin may still contribute to other aspects of oligodendrocyte biology, it is not essential for myelination and remyelination in the CNS.
Benninger
Yves
Y
Institute for Cell Biology, Department of Biology, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.
Colognato
Holly
H
Thurnherr
Tina
T
Franklin
Robin J M
RJ
Leone
Dino P
DP
Atanasoski
Suzana
S
Nave
Klaus-Armin
KA
Ffrench-Constant
Charles
C
Suter
Ueli
U
Relvas
João B
JB
D000818:Animals; D017209:Apoptosis; D001369:Axons / Q000502:physiology; D002470:Cell Survival; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D002531:Cerebellum / Q000502:physiology; D003337:Corpus Callosum / Q000378:metabolism / Q000502:physiology; D017353:Gene Deletion; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000502:physiology*; D009836:Oligodendroglia / Q000378:metabolism / Q000502:physiology*; D009900:Optic Nerve / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism / Q000502:physiology
D019012:Integrin beta1