The Small GTPase Rac1 Regulates Auditory Hair Cell Morphogenesis
Autor: | Gwenaëllle S.G. Géléoc, Xiaowei Lu, Cynthia M. Grimsley-Myers, Conor W. Sipe |
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Rok vydání: | 2009 |
Předmět: |
rac1 GTP-Binding Protein
Morphogenesis Biology Article Mice Pregnancy Hair Cells Auditory otorhinolaryngologic diseases medicine Animals Small GTPase Mechanotransduction Organ of Corti Cells Cultured Cochlea Mice Knockout General Neuroscience Neuropeptides Epithelial Cells Kinocilium Actin cytoskeleton rac GTP-Binding Proteins Cell biology Rac GTP-Binding Proteins medicine.anatomical_structure Animals Newborn Female sense organs |
Zdroj: | The Journal of Neuroscience. 29:15859-15869 |
ISSN: | 1529-2401 0270-6474 |
Popis: | Morphogenesis of sensory hair cells, in particular their mechanotransduction organelle, the stereociliary bundle, requires highly organized remodeling of the actin cytoskeleton. The roles of Rho family small GTPases during this process remain unknown. Here we show that deletion ofRac1in the otic epithelium resulted in severe defects in cochlear epithelial morphogenesis. The mutant cochlea was severely shortened with a reduced number of auditory hair cells and cellular organization of the auditory sensory epithelium was abnormal.Rac1mutant hair cells also displayed defects in planar cell polarity and morphogenesis of the stereociliary bundle, including bundle fragmentation or deformation, and mispositioning or absence of the kinocilium. We further demonstrate that a Rac–PAK (p21-activated kinase) signaling pathway mediates kinocilium–stereocilia interactions and is required for cohesion of the stereociliary bundle. Together, these results reveal a critical function of Rac1 in morphogenesis of the auditory sensory epithelium and stereociliary bundle. |
Databáze: | OpenAIRE |
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