Abstract
Proper cochlear hair cell array development and sensory apparatus positioning are achieved by planar cell polarity signaling. Effectors executing proper tissue development and maturation programs are largely unknown. We show that the actin nucleator Cobl is an important effector in postnatal refinement and maintenance of planar cell polarity. During the critical time of hearing onset, these polarity defects coincided with reduced F-actin beneath the sensory apparatus and with premature kinocilium retraction. These defects were accompanied by organizational defects of the pericentriolar scaffold that coincided with basal body and centriolar mispositionings. Importantly, the pericentriolar defects observed in Cobl KO mice were demonstrated to be actin polymerization dependent and calcium/calmodulin signaling dependent. Because Cobl KO phenotypes manifested postnatally, planar cell polarity is not solely an important developmental process. The Cobl-dependent planar cell polarity maintenance and refinement processes we describe here seem critical for hearing, as Cobl KO mice show deficient cochlear amplification.
Highlights
Establishment and changes of cell morphology and polarity depend on forces created by actin and microtubule cytoskeletal structures
While microtubule-based ciliary structures are indicative of planar cell polarity (PCP) and the orientation of outer hair cells (OHCs) stereociliar bundles in the cochlea precisely reflects PCP in the tissue (Kelley et al, 2009; Ezan and Montcouquiol, 2013), little is known about PCP effectors and about postnatal processes subsequent to classical embryonic PCP signaling
Cobl KO Impairs pericentriolar material (PCM)-Kinocilium Alignment and Causes Premature Kinocilium Retraction prior to Hearing Onset Second, we addressed whether the PCM disorganization would coincide with impairments in kinocilium linkage and subsequently with defects in kinocilium stability
Summary
Establishment and changes of cell morphology and polarity depend on forces created by actin and microtubule cytoskeletal structures. Embryonic planar cell polarity (PCP) plays a central role in tissue patterning (Montcouquiol et al, 2003; Curtin et al, 2003). PCP signaling, for example, brings about a preliminary alignment of outer hair cells (OHCs) in the inner ear and of their stereocilia bundles serving as mechanosensors. While microtubule-based ciliary structures are indicative of PCP and the orientation of OHC stereociliar bundles in the cochlea precisely reflects PCP in the tissue (Kelley et al, 2009; Ezan and Montcouquiol, 2013), little is known about PCP effectors and about postnatal processes subsequent to classical embryonic PCP signaling
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