title: Focal adhesion kinase (FAK): A regulator of CNS myelination.
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 (Fak(flox/flox): PLP/CreER(T) 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.
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA.
authors.forename: Audrey D
authors.initials: AD
authors.lastname: Forrest
authors.forename: Hilary E
authors.initials: HE
authors.lastname: Beggs
authors.forename: Louis F
authors.initials: LF
authors.lastname: Reichardt
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Dupree
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Colello
authors.forename: Babette
authors.initials: B
authors.lastname: Fuss
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology*; D048430:Cell Shape / Q000235:genetics; D003463:Cues; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D009900:Optic Nerve / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D013997:Time Factors
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases