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First published online July 24, 2009
doi: 10.1242/10.1242/dev.038679

Development 136, 2717-2724 (2009)
Published by The Company of Biologists 2009
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β1 integrins are required for normal CNS myelination and promote AKT-dependent myelin outgrowth

Claudia S. Barros1,*, Tom Nguyen2,*, Kathryn S. R. Spencer1, Akiko Nishiyama3, Holly Colognato2,{dagger} and Ulrich Müller1,{dagger}

1 The Scripps Research Institute, Department of Cell Biology, Institute of Childhood and Neglected Disease, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
2 Department of Pharmacology, State University of New York, Stony Brook, NY 11794, USA.
3 Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269, USA.

{dagger} Authors for correspondence (e-mails: colognato{at}pharm.stonybrook.edu; umueller{at}scripps.edu)

Accepted 11 June 2009

Oligodendrocytes in the central nervous system (CNS) produce myelin sheaths that insulate axons to ensure fast propagation of action potentials. β1 integrins regulate the myelination of peripheral nerves, but their function during the myelination of axonal tracts in the CNS is unclear. Here we show that genetically modified mice lacking β1 integrins in the CNS present a deficit in myelination but no defects in the development of the oligodendroglial lineage. Instead, in vitro data show that β1 integrins regulate the outgrowth of myelin sheaths. Oligodendrocytes derived from mutant mice are unable to efficiently extend myelin sheets and fail to activate AKT (also known as AKT1), a kinase that is crucial for axonal ensheathment. The inhibition of PTEN, a negative regulator of AKT, or the expression of a constitutively active form of AKT restores myelin outgrowth in cultured β1-deficient oligodendrocytes. Our data suggest that β1 integrins play an instructive role in CNS myelination by promoting myelin wrapping in a process that depends on AKT.

Key words: β1 integrins, Myelination, Oligodendrocytes, Mouse


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Development 2009 136: e1603. [Full Text]  



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Home page
 J. Cell Sci.Home page
C. S. Barros, T. Nguyen, K. S. R. Spencer, A. Nishiyama, H. Colognato, and U. Muller
! 1 integrins are required for normal CNS myelination and promote AKT-dependent myelin outgrowth
J. Cell Sci., August 15, 2009; 122(16): e1606 - e1606.
[Full Text]


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