The Rho GTPase Cell Division Cycle 42 Regulates Stereocilia Development in Cochlear Hair Cells
Open Access
- 22 October 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Cell and Developmental Biology
Abstract
Stereocilia are actin-based cell protrusions on the apical surface of inner ear hair cells, playing a pivotal role in hearing and balancing sensation. The development and maintenance of stereocilia is tightly regulated and deficits in this process usually lead to hearing or balancing disorders. The Rho GTPase cell division cycle 42 (CDC42) is a key regulator of the actin cytoskeleton. It has been reported to localize in the hair cell stereocilia and play important roles in stereocilia maintenance. In the present work, we utilized hair cell-specific Cdc42 knockout mice and CDC42 inhibitor ML141 to explore the role of CDC42 in stereocilia development. Our data show that stereocilia height and width as well as stereocilia resorption are affected in Cdc42-deficient cochlear hair cells when examined at postnatal day 8 (P8). Moreover, ML141 treatment leads to planar cell polarity (PCP) deficits in neonatal hair cells. We also show that overexpression of a constitutively active mutant CDC42 in cochlear hair cells leads to enhanced stereocilia developmental deficits. In conclusion, the present data suggest that CDC42 plays a pivotal role in regulating hair cell stereocilia development.Funding Information
- National Natural Science Foundation of China
- Natural Science Foundation of Shandong Province
This publication has 53 references indexed in Scilit:
- FCHSD1 and FCHSD2 Are Expressed in Hair Cell Stereocilia and Cuticular Plate and Regulate Actin Polymerization In VitroPLOS ONE, 2013
- Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthoodScientific Reports, 2012
- Multi-isotope imaging mass spectrometry reveals slow protein turnover in hair-cell stereociliaNature, 2012
- Eps8 Regulates Hair Bundle Length and Functional Maturation of Mammalian Auditory Hair CellsPLoS Biology, 2011
- Regulation of Stereocilia Length by Myosin XVa and Whirlin Depends on the Actin-Regulatory Protein Eps8Current Biology, 2011
- Auditory and vestibular hair cell stereocilia: relationship between functionality and inner ear diseaseThe Journal of Laryngology & Otology, 2011
- Generation and characterization of Atoh1‐Cre knock‐in mouse linegenesis, 2010
- The Small GTPase Rac1 Regulates Auditory Hair Cell MorphogenesisJournal of Neuroscience, 2009
- Localization of inner hair cell mechanotransducer channels using high-speed calcium imagingNature Neuroscience, 2009
- Gene Targeting of Cdc42 and Cdc42GAP Affirms the Critical Involvement of Cdc42 in Filopodia Induction, Directed Migration, and Proliferation in Primary Mouse Embryonic FibroblastsMolecular Biology of the Cell, 2006