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Publication : The small GTPase Rac1 regulates auditory hair cell morphogenesis.

First Author  Grimsley-Myers CM Year  2009
Journal  J Neurosci Volume  29
Issue  50 Pages  15859-69
PubMed ID  20016102 Mgi Jnum  J:157099
Mgi Id  MGI:4430014 Doi  10.1523/JNEUROSCI.3998-09.2009
Citation  Grimsley-Myers CM, et al. (2009) The small GTPase Rac1 regulates auditory hair cell morphogenesis. J Neurosci 29(50):15859-69
abstractText  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 of Rac1 in 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. Rac1 mutant 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.
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