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

被引:32
作者
Anttonen, Tommi [1 ]
Kirjavainen, Anna [1 ]
Belevich, Ilya [1 ]
Laos, Maarja [1 ]
Richardson, William D. [2 ]
Jokitalo, Eija [1 ]
Brakebusch, Cord [3 ]
Pirvola, Ulla [1 ]
机构
[1] Univ Helsinki, Inst Biotechnol, Helsinki 00014, Finland
[2] UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England
[3] Univ Copenhagen, Biotech Res & Innovat Ctr, Biomed Inst, DK-2200 Copenhagen, Denmark
基金
芬兰科学院;
关键词
FIBROBLAST-GROWTH-FACTOR; RETICULAR LAMINA; PILLAR CELLS; HAIR-CELLS; E-CADHERIN; ORGAN; CORTI; ACTIN; CDC42; JUNCTIONS;
D O I
10.1038/srep00978
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-ERT2 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 aPKC lambda/iota 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-a ctin 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.
引用
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页数:13
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