title: Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood.
abstract: Cdc42 regulates the initial establishment of cytoskeletal and junctional structures, but only little is known about its role at later stages of cellular differentiation. We studied Cdc42's role in vivo in auditory supporting cells, epithelial cells with high structural complexity. Cdc42 inactivation was induced early postnatally using the Cdc42(loxP/loxP);Fgfr3-iCre-ER(T2) mice. Cdc42 depletion impaired elongation of adherens junctions and F-actin belts, leading to constriction of the sensory epithelial surface. Fragmented F-actin belts, junctions containing ectopic lumens and misexpression of a basolateral membrane protein in the apical domain were observed. These defects and changes in aPKCλ/ι expression suggested that apical polarization is impaired. Following a lesion at adulthood, supporting cells with Cdc42 loss-induced maturational defects collapsed and failed to remodel F-actin belts, a process that is critical to scar formation. Thus, Cdc42 is required for structural differentiation of auditory supporting cells and this proper maturation is necessary for wound healing in adults.
authors.affiliation: Institute of Biotechnology, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Tommi
authors.initials: T
authors.lastname: Anttonen
authors.forename: Anna
authors.initials: A
authors.lastname: Kirjavainen
authors.forename: Ilya
authors.initials: I
authors.lastname: Belevich
authors.forename: Maarja
authors.initials: M
authors.lastname: Laos
authors.forename: William D
authors.initials: WD
authors.lastname: Richardson
authors.forename: Eija
authors.initials: E
authors.lastname: Jokitalo
authors.forename: Cord
authors.initials: C
authors.lastname: Brakebusch
authors.forename: Ulla
authors.initials: U
authors.lastname: Pirvola
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D006198:Hair Cells, Auditory / Q000473:pathology* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009925:Organ of Corti / Q000293:injuries* / Q000503:physiopathology*; D014945:Wound Healing / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D020764:cdc42 GTP-Binding Protein