About

David W. Raible is an Adjunct Professor in the Department of Biology at the University of Washington. His research focuses on the biology of hair cells in the inner ear, which act as mechanosensors converting mechanical stimuli into electrical signals for hearing and balance perception. He investigates why hair cells die, how they can be protected from damage, and how they regenerate, using the zebrafish system due to its ability to regenerate hair cells throughout life. Raible's work includes studying the patterning of zebrafish dermal appendages, mechanisms of hair cell regeneration, and cellular responses to environmental insults such as noise and chemicals. His background includes a B.A. from Cornell University obtained in 1983, a Ph.D. from the University of Pennsylvania in 1989, and postdoctoral research at the University of Oregon from 1990 to 1995.

Research topics

• Biology
• Cell biology
• Neuroscience
• Anatomy
• Genetics

Selected publications

• Activity and retinoic acid drive hair cell spatial patterning in the zebrafish utricle

  DRYAD · 2026-02-04 · 1 citations

  datasetOpen accessSenior author

  The zebrafish vestibular otolith organs, like those of other vertebrate species, are organized into central (striolar) and peripheral (extrastriolar) zones that drive different vestibular circuits. How and when these hair cell patterns develop in the zebrafish is unknown. We determined that early-developing hair cells (<36 hours) expressed both striolar and extrastriolar transcriptomic markers. After 36 hours, these hair cells specify into extrastriolar hair cells. Later-developing hair cells (>36 hours) mostly develop directly as striolar or extrastriolar. We observed complementary patterns of RA degrading and synthesizing enzymes that colocalize with striolar and extrastriolar zones, respectively, suggesting evolutionarily conserved molecular signaling. RA treatment during development increased the relative proportion of extrastriolar and intermediate-type hair cells, indicating that enriched RA reduces striolar development. However, in fish with mechanotransduction dysfunction from a cdh23 mutation, normal RA patterning is insufficient to finalize the fate of early-born hair cells, which remain transcriptomically unresolved. RA treatment further exacerbates abnormal patterning. Therefore, we conclude that hair cell fate, and thus normal zonal patterning, depends on both hair cell activity and the RA gradient.

  PublisherDOI

• Activity and retinoic acid drive hair cell spatial patterning in the zebrafish utricle

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-18 · 1 citations

  preprintOpen accessSenior author

  Abstract The zebrafish vestibular otolith organs, like those of other vertebrate species, are organized into central (striolar) and peripheral (extrastriolar) zones that drive different vestibular circuits. How and when these spatial hair cell patterns develop in the zebrafish is unknown. We determined that early-developing hair cells (<36 hours) expressed both striolar and extrastriolar transcriptomic markers. After 36 hours, these hair cells become specified as extrastriolar hair cells. Later-developing hair cells (>36 hours) mostly develop directly as striolar or extrastriolar. We observed complementary patterns of RA degrading and synthesizing enzymes that colocalize with striolar and extrastriolar hair cells, respectively, indicating evolutionarily conserved molecular signaling. RA treatment during development increased the proportion of extrastriolar and intermediate-type hair cells, indicating that increased RA reduces striolar development. However, in fish with mechanotransduction dysfunction from a cadherin23 mutation, normal RA patterning is insufficient to finalize the fate of early-born hair cells, which remain transcriptomically unresolved. RA treatment further exacerbates this abnormal patterning. We conclude that hair cell fate, and thus normal zonal patterning, depends on both hair cell activity and the RA gradient. Summary statement The development of hair cell zonal patterning in the vestibular sensory epithelia depends on a balance of mechanotransduction-driven activity and retinoic acid.

  PublisherOA PDFDOI

• Multiple mechanisms of aminoglycoside ototoxicity are distinguished by subcellular localization of action

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-05-31

  preprintOpen accessSenior authorCorresponding

  Mechanosensory hair cells of the inner ears and lateral line of vertebrates display heightened vulnerability to environmental insult, with damage resulting in hearing and balance disorders. An important example is hair cell loss due to exposure to toxic agents including therapeutic drugs such as the aminoglycoside antibiotics such as neomycin and gentamicin and antineoplastic agents. We describe two distinct cellular pathways for aminoglycoside-induced hair cell death in zebrafish lateral line hair cells. Neomycin exposure results in death from acute exposure with most cells dying within 1 hour of exposure. By contrast, exposure to gentamicin results primarily in delayed hair cell death, taking up to 24 hours for maximal effect. Washout experiments demonstrate that delayed death does not require continuous exposure, demonstrating two mechanisms where downstream responses differ in their timing. Acute damage is associated with mitochondrial calcium fluxes and can be alleviated by the mitochondrially-targeted antioxidant mitoTEMPO, while delayed death is independent of these factors. Conversely delayed death is associated with lysosomal accumulation and is reduced by altering endolysosomal function, while acute death is not sensitive to lysosomal manipulations. These experiments reveal the complexity of responses of hair cells to closely related compounds, suggesting that intervention focusing on early events rather than specific death pathways may be a successful therapeutic strategy.

  PublisherOA PDFDOI

• Zebrafish in-vivo study reveals deleterious activity of human TBC1D24 genetic variants linked with autosomal dominant hearing loss

  Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · 2024-11-23 · 2 citations

  article
  PublisherDOI

• Decision letter: Atoh1 is required for the formation of lateral line electroreceptors and hair cells, whereas FoxG1 represses an electrosensory fate

  2024-04-26

  peer-reviewOpen accessSenior author

  Targeting Atoh1 for CRISPR/Cas9-mediated mutagenesis in sturgeon results in missing electroreceptors as well as mechanosensory hair cells, supporting conserved developmental mechanisms, whereas ectopic electrosensory organs develop after targeting mechanosensory-restricted Foxg1, suggesting FoxG1 directly or indirectly represses electrosensory organ formation.

  PublisherDOI

• Spherical harmonics analysis reveals cell shape-fate relationships in zebrafish lateral line neuromasts

  Development · 2024-01-15 · 13 citations

  articleOpen accessSenior author

  Cell shape is a powerful readout of cell state, fate, and function. We describe a custom workflow to perform semi-automated, 3D cell and nucleus segmentation, and spherical harmonics and principal components analysis to distill cell and nuclear shape variation into discrete biologically meaningful parameters. We apply these methods to analyze shape in neuromast cells of the zebrafish lateral line system, finding shapes vary with cell location and identity. The distinction between hair cells and support cells accounted for much of the variation, which allowed us to train classifiers to predict cell identity from shape features. Using transgenic markers for support cell subpopulations, we found that subtypes had different shapes from each other. To investigate how loss of a neuromast cell type altered cell shape distributions, we examined atoh1a mutants that lack hair cells. We found that mutant neuromasts lacked the cell shape phenotype associated with hair cells, but did not exhibit a mutant-specific cell shape. Our results demonstrate the utility of using 3D cell shape features to characterize, compare, and classify cells in a living, developing organism.

  PublisherOA PDFDOI

• Transdifferentiation is temporally uncoupled from progenitor pool expansion during hair cell regeneration in the zebrafish inner ear

  Development · 2024-07-24 · 10 citations

  articleOpen accessSenior author

  Death of mechanosensory hair cells in the inner ear is a common cause of auditory and vestibular impairment in mammals, which have a limited ability to regrow these cells after damage. In contrast, non-mammalian vertebrates, including zebrafish, can robustly regenerate hair cells after severe organ damage. The zebrafish inner ear provides an understudied model system for understanding hair cell regeneration in organs that are highly conserved with their mammalian counterparts. Here, we quantitatively examine hair cell addition during growth and regeneration of the larval zebrafish inner ear. We used a genetically encoded ablation method to induce hair cell death and we observed gradual regeneration with correct spatial patterning over a 2-week period following ablation. Supporting cells, which surround and are a source of new hair cells, divide in response to hair cell ablation, expanding the possible progenitor pool. In parallel, nascent hair cells arise from direct transdifferentiation of progenitor pool cells temporally uncoupled from supporting cell division. These findings reveal a previously unrecognized mechanism of hair cell regeneration with implications for how hair cells may be encouraged to regenerate in the mammalian ear.

  PublisherDOI

• eLife assessment: Semaphorin7A patterns neural circuitry in the lateral line of the zebrafish

  2024-08-12

  peer-reviewOpen access1st authorCorresponding
  PublisherDOI

• eLife Assessment: Semaphorin7A patterns neural circuitry in the lateral line of the zebrafish

  2024-04-08

  peer-reviewOpen access1st authorCorresponding

  In a developing nervous system, axonal arbors often undergo complex rearrangements before neural circuits attain their final innervation topology. In the lateral line sensory system of the zebrafish, developing sensory axons reorganize their terminal arborization patterns to establish precise neural microcircuits around the mechanosensory hair cells. However, a quantitative understanding of the changes in the sensory arbor morphology and the regulators behind the microcircuit assembly remain enigmatic. Here, we report that Semaphorin7A (Sema7A) acts as an important mediator of these processes. Utilizing a semi-automated three-dimensional neurite tracing methodology and computational techniques, we have identified and quantitatively analyzed distinct topological features that shape the network in wild-type and Sema7A loss-of-function mutants. In contrast to those of wild-type animals, the sensory axons in Sema7A mutants display aberrant arborizations with disorganized network topology and diminished contacts to hair cells. Moreover, ectopic expression of a secreted form of Sema7A by non-hair cells induces chemotropic guidance of sensory axons. Our findings propose that Sema7A likely functions both as a juxtracrine and as a secreted cue to pattern neural circuitry during sensory organ development.

  PublisherDOI

• Transdifferentiation is uncoupled from progenitor pool expansion during hair cell regeneration in the zebrafish inner ear

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-04-11 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Death of mechanosensory hair cells in the inner ear is a common cause of auditory and vestibular impairment in mammals, which have a limited ability to regrow these cells after damage. In contrast, non-mammalian vertebrates including zebrafish can robustly regenerate hair cells following severe organ damage. The zebrafish inner ear provides an understudied model system for understanding hair cell regeneration in organs that are highly conserved with their mammalian counterparts. Here we quantitatively examine hair cell addition during growth and regeneration of the larval zebrafish inner ear. We used a genetically encoded ablation method to induce hair cell death and observed gradual regeneration with correct spatial patterning over two weeks following ablation. Supporting cells, which surround and are a source of new hair cells, divide in response to hair cell ablation, expanding the possible progenitor pool. In parallel, nascent hair cells arise from direct transdifferentiation of progenitor pool cells uncoupled from progenitor division. These findings reveal a previously unrecognized mechanism of hair cell regeneration with implications for how hair cells may be encouraged to regenerate in the mammalian ear.

  PublisherOA PDFDOI

Recent grants

• NIH Grant S10RR026826

  NIH · $500k · 2011

• NIH Grant R01NS035833

  NIH · $1.6M · 2004

• NIH Grant U01NS074506

  NIH · $516k · 2016

• NIH Grant R01DC013688

  NIH · $296k · 2016

• NIH Grant R21DC015110

  NIH · $426k · 2018

Frequent coauthors

• Edwin W. Rubel

  University of Washington

  55 shared

• JG Schembri

  Columbia University Irving Medical Center

  36 shared

• Fernando Alvarez

  36 shared

• D D Sabatini

  36 shared

• DR Colman

  36 shared

• E M Norgård

  Columbia University Irving Medical Center

  36 shared

• L. Bernier

  Hospital Universitario de Guadalajara

  36 shared

• Alejandro Mentaberry

  University of Buenos Aires

  36 shared

Labs

• Raible LabPI