Focal adhesion kinase (FAK): A regulator of CNS myelination
- 17 February 2009
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 87 (15), 3456-3464
- https://doi.org/10.1002/jnr.22022
Abstract
The formation of the myelin sheath is a crucial step during development because it enables fast and efficient propagation of signals within the limited space of the mammalian central nervous system (CNS). During the process of myelination, oligodendrocytes actively interact with the extracellular matrix (ECM). These interactions are considered crucial for proper and timely completion of the myelin sheath. However, the exact regulatory circuits involved in the signaling events that occur between the ECM and oligodendrocytes are currently not fully understood. Therefore, in the present study we investigated the role of a known integrator of cell–ECM signaling, namely, focal adhesion kinase (FAK), in CNS myelination via the use of conditional (oligodendrocyte‐specific) and inducible FAK‐knockout mice (Fakflox/flox: PLP/CreERT mice). When inducing FAK knockout just prior to and during active myelination of the optic nerve, we observed a significant reduction in the number of myelinated fibers on postnatal day 14. In addition, our data revealed a decreased number of primary processes extending from oligodendrocyte cell bodies at this postnatal age and on induction of FAK knockout. In contrast, myelination appeared normal on postnatal day 28. Thus, our data suggest that FAK controls the efficiency and timing of CNS myelination during its initial stages, at least in part, by regulating oligodendrocyte process outgrowth and/or remodeling.Keywords
This publication has 79 references indexed in Scilit:
- Dual Functional Activity of Semaphorin 3B Is Required for Positioning the Anterior CommissureNeuron, 2005
- Focal adhesion kinase: in command and control of cell motilityNature Reviews Molecular Cell Biology, 2005
- Phosphodiesterase-Iα/autotaxin controls cytoskeletal organization and FAK phosphorylation during myelinationMolecular and Cellular Neuroscience, 2004
- Integrin-linked kinase is required for laminin-2–induced oligodendrocyte cell spreading and CNS myelinationThe Journal of cell biology, 2003
- Normal CNS Myelination in Transgenic Mice Overexpressing MHC Class I H-2Ld in OligodendrocytesMolecular and Cellular Neuroscience, 2001
- Signaling through focal adhesion kinaseBioEssays, 1997
- Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient miceNature, 1995
- Focal Adhesion Kinase Is Not Essential for in Vitro and in Vivo Differentiation of ES CellsBiochemical and Biophysical Research Communications, 1995
- A Protein Involved in Central Nervous System Myelination: Localization in the Extracellular Matrix and Induction in Neuroblastoma CellsDevelopmental Neuroscience, 1994
- A myelin proteolipid protein-LacZ fusion protein is developmentally regulated and targeted to the myelin membrane in transgenic mice.The Journal of cell biology, 1993