Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood
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Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood. / Anttonen, Tommi; Kirjavainen, Anna; Belevich, Ilya; Laos, Maarja; Richardson, William D; Jokitalo, Eija; Brakebusch, Cord Herbert; Pirvola, Ulla.
In: Scientific Reports, Vol. 2, 2012, p. 978.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 2
SP - 978
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
ER -
ID: 108162644