Cytoskeletal stability in the auditory organ in vivo: RhoA is dispensable for wound healing but essential for hair cell development
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Cytoskeletal stability in the auditory organ in vivo : RhoA is dispensable for wound healing but essential for hair cell development. / Anttonen, Tommi; Belevich, Ilya; Laos, Maarja; Herranen, Anni; Jokitalo, Eija; Brakebusch, Cord; Pirvola, Ulla.
In: eNeuro, Vol. 4, No. 5, e0149-17.2017, 2017.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cytoskeletal stability in the auditory organ in vivo
T2 - RhoA is dispensable for wound healing but essential for hair cell development
AU - Anttonen, Tommi
AU - Belevich, Ilya
AU - Laos, Maarja
AU - Herranen, Anni
AU - Jokitalo, Eija
AU - Brakebusch, Cord
AU - Pirvola, Ulla
PY - 2017
Y1 - 2017
N2 - Wound healing in the inner ear sensory epithelia is performed by the apical domains of supporting cells (SCs). Junctional F-actin belts of SCs are thin during development but become exceptionally thick during maturation. The functional significance of the thick belts is not fully understood. We have studied the role of F-actin belts during wound healing in the developing and adult cochlea of mice in vivo. We show that the thick belts serve as intracellular scaffolds that preserve the positions of surviving cells in the cochlear sensory epithelium. Junctions associated with the thick F-actin belts did not readily disassemble during wound healing. To compensate for this, basolateral membranes of SCs participated in the closure of surface breach. Because not only neighboring but also distant SCs contributed to wound healing by basolateral protrusions, this event appears to be triggered by contact-independent diffusible signals. In the search for regulators of wound healing, we inactivated RhoA in SCs, which, however, did not limit wound healing. RhoA inactivation in developing outer hair cells (OHCs) caused myosin II delocalization from the perijunctional domain and apical cell-surface enlargement. These abnormalities led to the extrusion of OHCs from the epithelium. These results demonstrate the importance of stability of the apical domain, both in wound repair by SCs and in development of OHCs, and that only this latter function is regulated by RhoA. Because the correct cytoarchitecture of the cochlear sensory epithelium is required for normal hearing, the stability of cell apices should be maintained in regenerative and protective interventions.
AB - Wound healing in the inner ear sensory epithelia is performed by the apical domains of supporting cells (SCs). Junctional F-actin belts of SCs are thin during development but become exceptionally thick during maturation. The functional significance of the thick belts is not fully understood. We have studied the role of F-actin belts during wound healing in the developing and adult cochlea of mice in vivo. We show that the thick belts serve as intracellular scaffolds that preserve the positions of surviving cells in the cochlear sensory epithelium. Junctions associated with the thick F-actin belts did not readily disassemble during wound healing. To compensate for this, basolateral membranes of SCs participated in the closure of surface breach. Because not only neighboring but also distant SCs contributed to wound healing by basolateral protrusions, this event appears to be triggered by contact-independent diffusible signals. In the search for regulators of wound healing, we inactivated RhoA in SCs, which, however, did not limit wound healing. RhoA inactivation in developing outer hair cells (OHCs) caused myosin II delocalization from the perijunctional domain and apical cell-surface enlargement. These abnormalities led to the extrusion of OHCs from the epithelium. These results demonstrate the importance of stability of the apical domain, both in wound repair by SCs and in development of OHCs, and that only this latter function is regulated by RhoA. Because the correct cytoarchitecture of the cochlear sensory epithelium is required for normal hearing, the stability of cell apices should be maintained in regenerative and protective interventions.
KW - Auditory
KW - Cytoskeleton
KW - Development
KW - Inner ear
KW - RhoA
KW - Wound healing
U2 - 10.1523/ENEURO.0149-17.2017
DO - 10.1523/ENEURO.0149-17.2017
M3 - Journal article
C2 - 28929130
AN - SCOPUS:85032158195
VL - 4
JO - eNeuro
JF - eNeuro
SN - 2373-2822
IS - 5
M1 - e0149-17.2017
ER -
ID: 185445819