Prolonged exposure to loud noise has been shown to affect inner ear sensory hair cells in a variety of deleterious manners, including damaging the stereocilia core. The damaged sites can be visualized as ‘gaps’ in phalloidin staining of F-actin, and the enrichment of monomeric actin at these sites, along with an actin nucleator and crosslinker, suggests that localized remodeling occurs to repair the broken filaments. Herein, we show that gaps in mouse auditory hair cells are largely repaired within 1 week of traumatic noise exposure through the incorporation of newly synthesized actin. We provide evidence that Xin actin binding repeat containing 2 (XIRP2) is required for the repair process and facilitates the enrichment of monomeric γ-actin at gaps. Recruitment of XIRP2 to stereocilia gaps and stress fiber strain sites in fibroblasts is force-dependent, mediated by a novel mechanosensor domain located in the C-terminus of XIRP2. Our study describes a novel process by which hair cells can recover from sublethal hair bundle damage and which may contribute to recovery from temporary hearing threshold shifts and the prevention of age-related hearing loss.
more »
« less
Noise-induced distortion of the mean limit cycle of nonlinear oscillators
We study the change in the size and shape of the mean limit cycle of a stochastically driven nonlinear oscillator as a function of noise amplitude. Such dynamics occur in a variety of nonequilibrium systems, including the spontaneous oscillations of hair cells of the inner ear. The noise-induced distortion of the limit cycle generically leads to its rounding through the elimination of sharp (high-curvature) features through a process we call corner cutting. We provide a criterion that may be used to identify limit cycle regions most susceptible to such noise-induced distortions. By using this criterion, one may obtain more meaningful parametric fits of nonlinear dynamical models from noisy experimental data, such as those coming from spontaneously oscillating hair cells.
more »
« less
- Award ID(s):
- 1709785
- PAR ID:
- 10133417
- Date Published:
- Journal Name:
- Physical review and Physical review letters index
- Volume:
- 99
- ISSN:
- 0094-0003
- Page Range / eLocation ID:
- 062124
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Diversification of cnidarian mechanosensory neurons across life cycle phases: evidence from HydrozoaOver the course of more than half a billion years of independent evolution, cnidarians (e.g. sea anemones, corals and jellyfishes) have evolved diverse, multicellular, mechanosensory structures ranging from tentacles of hydroids to gravity-sensors of moon jellyfish. The ectodermal epithelium of mechanosensory structures houses the mechanosensory neuron – known as the concentric hair cell – characterized by an apical mechanosensory apparatus consisting of a single cilium surrounded by one or multiple rings of microvilli/stereovilli. While distinct concentric hair cell types are known to occur within life-cycle-stage-specific structures such as the sea anemone tentacles, it is unclear whether diverse concentric hair cell types exist across life cycle phases of any cnidarian. Here we report evidence from the hydrozoan Cladonema pacificum that concentric hair cells of sedentary polyps are distinct from those of free-swimming medusae. By carrying out touch assays, we demonstrate that polyps and medusae exhibit distinct mechanosensory behaviors. Moreover, we find that concentric hair cells in the ectodermal epithelium of touch-sensitive regions in polyps differ from those in medusae in the morphology of apical sensory apparatuses. Furthermore, polyp-type concentric hair cells are not retained in the ectoderm of medusa buds, and medusa-type concentric hair cells begin to form de novo during medusa formation. Taken together, these findings suggest that distinct mechanosensitive behaviors of polyps and medusae are mediated by morphologically different sets of mechanosensory neurons that develop via life-cycle-stage-specific mechanisms. We propose that cell type diversification of mechanosensory neurons occurred not only within a given life cycle phase but across life cycle phases in cnidarian evolution.more » « less
-
Abstract Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration 1 . Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi 2,3 , we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue 4 , we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.more » « less
-
Abstract Hair cells of the auditory and vestibular systems are capable of detecting sounds that induce sub-nanometer vibrations of the hair bundle, below the stochastic noise levels of the surrounding fluid. Furthermore, the auditory system exhibits a highly rapid response time, in the sub-millisecond regime. We propose that chaotic dynamics enhance the sensitivity and temporal resolution of the hair bundle response, and we provide experimental and theoretical evidence for this effect. We use the Kolmogorov entropy to measure the degree of chaos in the system and the transfer entropy to quantify the amount of stimulus information captured by the detector. By varying the viscosity and ionic composition of the surrounding fluid, we are able to experimentally modulate the degree of chaos observed in the hair bundle dynamicsin vitro. We consistently find that the hair bundle is most sensitive to a stimulus of small amplitude when it is poised in the weakly chaotic regime. Further, we show that the response time to a force step decreases with increasing levels of chaos. These results agree well with our numerical simulations of a chaotic Hopf oscillator and suggest that chaos may be responsible for the high sensitivity and rapid temporal response of hair cells.more » « less
-
Hair cells are the principal sensory receptors of the vertebrate auditory system, where they transduce sounds through mechanically gated ion channels that permit cations to flow from the surrounding endolymph into the cells. The lateral line of zebrafish has served as a key model system for understanding hair cell physiology and development, often with the belief that these hair cells employ a similar transduction mechanism. In this study, we demonstrate that these hair cells are exposed to an unregulated external environment with cation concentrations that are too low to support transduction. Our results indicate that hair cell excitation is instead mediated by a substantially different mechanism involving the outward flow of anions. Further investigation of hair cell transduction in a diversity of sensory systems and species will likely yield deep insights into the physiology of these unique cells.more » « less
An official website of the United States government

