Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood

TY - JOUR

T1 - Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood

AU - Anttonen, Tommi

AU - Kirjavainen, Anna

AU - Belevich, Ilya

AU - Laos, Maarja

AU - Richardson, William D

AU - Jokitalo, Eija

AU - Brakebusch, Cord Herbert

AU - Pirvola, Ulla

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Aging

KW - Animals

KW - Cells, Cultured

KW - Hair Cells, Auditory

KW - Mice

KW - Mice, Knockout

KW - Organ of Corti

KW - Wound Healing

KW - cdc42 GTP-Binding Protein

U2 - 10.1038/srep00978

DO - 10.1038/srep00978

M3 - Journal article

C2 - 23248743

SN - 2045-2322

VL - 2

SP - 978

JO - Scientific Reports

JF - Scientific Reports

ER -