Emerging Roles of RNA-Binding Proteins in Inner Ear Hair Cell Development and Regeneration

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(20), С. 12393 - 12393

Опубликована: Окт. 16, 2022

RNA-binding proteins (RBPs) regulate gene expression at the post-transcriptional level. They play major roles in tissue- and stage-specific of protein isoforms as well maintenance homeostasis. The inner ear is a bi-functional organ, with cochlea vestibular system required for hearing maintaining balance, respectively. It relatively documented that transcription factors signaling pathways are critically involved formation structures development hair cells. Accumulating evidence highlights emerging functions RBPs regulation cell function. Importantly, mutations splicing RBP family defective alternative splicing, which result inappropriate isoforms, lead to deafness both animal models humans. Because critical regulators proliferation differentiation, they present potential promote regeneration following noise- or ototoxin-induced damage through mitotic non-mitotic mechanisms. Therefore, deciphering RBP-regulated events during can help define therapeutic strategies treatment loss. In this review, we outline our evolving understanding implications disease aim promoting future research field.

Язык: Английский

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Recent advances in Otology: Current landscape and future direction

Auris Nasus Larynx, Год журнала: 2024, Номер 51(3), С. 605 - 616

Опубликована: Март 29, 2024

Язык: Английский

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Comparative biology of the amniote vestibular utricle

Hearing Research, Год журнала: 2024, Номер 448, С. 109035 - 109035

Опубликована: Май 19, 2024

The sensory epithelia of the auditory and vestibular systems vertebrates have shared developmental evolutionary histories. However, while show great variation across vertebrates, appear seemingly more conserved. An exploration current knowledge comparative biology amniote utricle, a epithelium that senses linear acceleration, shows interesting instances variability between birds mammals. distribution hair cell types, position line bundle polarity reversal properties supporting cells marked differences, likely impacting function regeneration potential.

Язык: Английский

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Junctional Force Patterning drives both Positional and Orientational Order in Auditory Epithelia

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Март 3, 2023

Abstract For physiological function, organs must organise constituent cell types in precise spatial and orientational order. While single-cell type epithelia, morphogenesis is driven by forces exerted at junctions 1-3, it not known whether can drive the acquisition of patterns polarity comprising multiple types. We investigate process global alignment avian auditory epithelium. This consists two types, hair cells (HCs), with an asymmetric mechanosensory bundle on its apex, supporting (SCs) 4. During development, these form a regular pattern, each HC aligns tissue axis. Through combination experiments theory, we find that tissue-wide force patterning generates both positional Positional order established differences between mechanical activity cell-cell junctions. These are encoded cell-specific genetic programmes restricting di-phosphorylated non-muscle myosin-II regulatory light chain (RLC) to specific Importantly, organises supracellular myosin through local attenuation RLC phosphorylation, generating across entire tissue. Our findings show junctional asymmetries couple rearrangements polarity, potentially fundamental feature development repair tissues consisting different

Язык: Английский

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Region-specific reversal of epidermal planar polarity in the rosette fancy mouse

Development, Год журнала: 2023, Номер 150(17)

Опубликована: Авг. 25, 2023

The planar cell polarity (PCP) pathway collectively orients cells with respect to a body axis. Hair follicles of the murine epidermis provide striking readout PCP activity in their uniform alignment across skin. Here, we characterize, from molecular tissue-scale, establishment rosette fancy mouse, natural variant posterior-specific whorls its fur, understand how epidermal is coordinated tissue. We find that hair emerge reversed orientations specifically posterior region, creating mirror image polarity. trait associated missense mutation core gene Fzd6, which alters consensus site for N-linked glycosylation, inhibiting membrane localization. Unexpectedly, Fzd6 trafficking defect does not block asymmetric localization other proteins. Rather, normally axis asymmetry rotates where PCP-directed movements orient are reversed, suggesting 180°. Collectively, our multiscale analysis reveals patterning can be regionally decoupled produce mouse.

Язык: Английский

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Core PCP mutations affect short time mechanical properties but not tissue morphogenesis in theDrosophilapupal wing

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Дек. 10, 2022

Abstract How morphogenetic movements are robustly coordinated in space and time is a fundamental open question biology. We study this using the wing of Drosophila melanogaster , an epithelial tissue that undergoes large-scale flows during pupal stages. showed previously (Etournay et al., 2015) morphogenesis involves both cellular behaviors allow relaxation mechanical stress, as well appear to be actively patterned. The core planar cell polarity (PCP) pathway influences many other contexts, which suggests it could globally pattern active morphogenesis. show here, however, not case: there no significant phenotype on dynamics underlying mutants PCP. Furthermore, laser ablation experiments, coupled with rheological model describe response ablation, we conclude while PCP mutations affect fast timescale they do overall mechanics. In conclusion, our work shows shape changes independent one potential chemical guiding cue,

Язык: Английский

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Core PCP mutations affect short-time mechanical properties but not tissue morphogenesis in the Drosophila pupal wing

eLife, Год журнала: 2023, Номер 12

Опубликована: Дек. 20, 2023

How morphogenetic movements are robustly coordinated in space and time is a fundamental open question biology. We study this using the wing of Drosophila melanogaster , an epithelial tissue that undergoes large-scale flows during pupal stages. Previously, we showed morphogenesis involves both cellular behaviors allow relaxation mechanical stress, as well appear to be actively patterned (Etournay et al., 2015). Here, show these active not guided by core planar cell polarity (PCP) pathway, conserved signaling system guides development many other contexts. find no significant phenotype on dynamics underlying mutants PCP. Furthermore, laser ablation experiments, coupled with rheological model describe response ablation, conclude while PCP mutations affect fast timescale they do significantly overall mechanics. In conclusion, our work shows shape changes require orientational guiding cue.

Язык: Английский

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Emergence of planar cell polarity from the interplay of local interactions and global gradients

eLife, Год журнала: 2024, Номер 13

Опубликована: Окт. 25, 2024

Planar cell polarity (PCP) - tissue-scale alignment of the direction asymmetric localization proteins at cell-cell interface is essential for embryonic development and physiological functions. Abnormalities in PCP can result developmental imperfections, including neural tube closure defects misaligned hair follicles. Decoding mechanisms responsible establishment maintenance remains a fundamental open question. While roles various molecules broadly classified into 'global' 'local' modules have been well-studied, their necessity sufficiency explaining connecting perturbations to experimentally observed patterns not examined. Here, we develop minimal model that captures proposed features global tissue-level gradient local distribution protein complexes. The suggests while emerge without gradient, only acts as cue but also increases robustness against stochastic perturbations. We recapitulated quantified swirling domineering non-autonomy, using three free parameters rate binding membrane, concentration proteins, steepness. explain how self-stabilizing localizations presence lead robust reveal design principles polarized system.

Язык: Английский

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Distribution of ciliary adaptor proteins tubby and TULP3 in the organ of Corti

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Апрель 18, 2023

Tubby-like proteins are membrane-associated adaptors that mediate directional trafficking into primary cilia. In inner ear sensory epithelia, cilia-including the hair cell's kinocilium-play important roles as organizers of polarity, tissue architecture and cellular function. However, auditory dysfunction in tubby mutant mice was recently found to be related a non-ciliary function tubby, organization protein complex bundles outer cells (OHCs). Targeting signaling components cilia cochlea might therefore rather rely on closely tubby-like (TULPs). this study, we compared subcellular localization TULP3 mouse organs. Immunofluorescence microscopy confirmed previously reported highly selective stereocilia tips OHCs revealed unnoticed transient kinocilia during early postnatal development. detected organ Corti vestibular epithelium, where it displayed spatiotemporal pattern. localized cochlear development but disappeared subsequently before onset hearing. This pattern suggested role targeting ciliary kinocilia, possibly developmental processes shape epithelia. Concurrent with loss from pronounced immunolabeling progressively appeared at microtubule non-sensory Pillar (PCs) Deiters (DC). may indicate novel TULP associated formation or regulation microtubule-based structures.

Язык: Английский

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Local coordination of epithelial planar polarity in the maintenance and regeneration of the adult rat airway

Cell and Tissue Research, Год журнала: 2023, Номер 394(1), С. 163 - 175

Опубликована: Июль 18, 2023

Язык: Английский

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