scholarly journals Live imaging of hair bundle polarity acquisition demonstrates a critical timeline for transcription factor Emx2

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Yosuke Tona ◽  
Doris K Wu
Keyword(s):  
Transcription Factor ◽  
Hair Cells ◽  
Time Window ◽  
Critical Time ◽  
Live Imaging ◽  
Hair Bundle ◽  
Directional Sensitivity ◽  
Mother Centriole ◽  
Daughter Centriole

Directional sensitivity of hair cells (HCs) is conferred by the aymmetric apical hair bundle, comprised of a kinocilium and stereocilia staircase. The mother centriole (MC) forms the base of the kinocilium and the stereocilia develop adjacent to it. Previously, we showed that transcription factor Emx2 reverses hair bundle orientation and its expression in the mouse vestibular utricle is restricted, resulting in two regions of opposite bundle orientation (Jiang et al., 2017). Here, we investigated establishment of opposite bundle orientation in embryonic utricles by live-imaging GFP-labeled centrioles in HCs. The daughter centriole invariably migrated ahead of the MC from the center to their respective peripheral locations in HCs. Comparing HCs between utricular regions, centriole trajectories were similar but they migrated toward opposite directions, suggesting that Emx2 pre-patterned HCs prior to centriole migration. Ectopic Emx2, however, reversed centriole trajectory within hours during a critical time-window when centriole trajectory was responsive to Emx2.

scholarly journals Live imaging of hair bundle polarity acquisition in the mouse utricle demonstrates a critical timeline for transcription factor Emx2

2020 ◽  
Author(s):  
Yosuke Tona ◽  
Doris K. Wu
Keyword(s):  
Transcription Factor ◽  
Hair Cells ◽  
Time Window ◽  
Critical Time ◽  
Live Imaging ◽  
Hair Bundle ◽  
Directional Sensitivity ◽  
Mother Centriole ◽  
Daughter Centriole

ABSTRACTThe asymmetric hair bundle on top of hair cells (HCs), comprises a kinocilium and stereocilia staircase, dictates HC directional sensitivity. The mother centriole (MC) forms the base of the kinocilium, where stereocilia are subsequently built next to it. Previously we showed that transcription factor Emx2 reverses hair bundle orientation and its expression in the mouse vestibular utricle is restricted, resulting in two regions of opposite bundle orientation (Jiang et al, 2017). Here, we investigated establishment of opposite bundle orientation in embryonic utricles by live-imaging GFP-labeled centrioles in HCs. The daughter centriole invariably migrated ahead of the MC from the center to their respective peripheral locations in HCs. Comparing HCs between utricular regions, centriole trajectories were similar but they migrated towards opposite directions, suggesting that Emx2 pre-patterned HCs prior to centriole migration. Ectopic Emx2, however, reversed centriole trajectory within hours during a critical time-window when centriole trajectory was responsive to Emx2.

scholarly journals A Reversal in Hair Cell Orientation Organizes Both the Auditory and Vestibular Organs

2021 ◽  
Vol 15 ◽  
Author(s):  
Basile Tarchini
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Sensory Epithelium ◽  
Mirror Image ◽  
Hair Bundle ◽  
Directional Sensitivity ◽  
Mechanical Stimuli ◽  
Cell Orientation ◽  
Auditory Hair Cells ◽  
Organ Level

Sensory hair cells detect mechanical stimuli with their hair bundle, an asymmetrical brush of actin-based membrane protrusions, or stereocilia. At the single cell level, stereocilia are organized in rows of graded heights that confer the hair bundle with intrinsic directional sensitivity. At the organ level, each hair cell is precisely oriented so that its intrinsic directional sensitivity matches the direction of mechanical stimuli reaching the sensory epithelium. Coordinated orientation among neighboring hair cells usually ensures the delivery of a coherent local group response. Accordingly, hair cell orientation is locally uniform in the auditory and vestibular cristae epithelia in birds and mammals. However, an exception to this rule is found in the vestibular macular organs, and in fish lateral line neuromasts, where two hair cell populations show opposing orientations. This mirror-image hair cell organization confers bidirectional sensitivity at the organ level. Here I review our current understanding of the molecular machinery that produces mirror-image organization through a regional reversal of hair cell orientation. Interestingly, recent evidence suggests that auditory hair cells adopt their normal uniform orientation through a global reversal mechanism similar to the one at work regionally in macular and neuromast organs. Macular and auditory organs thus appear to be patterned more similarly than previously appreciated during inner ear development.

scholarly journals Transcription factor Emx2 controls stereociliary bundle orientation of sensory hair cells

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Tao Jiang ◽  
Katie Kindt ◽  
Doris K Wu
Keyword(s):  
Transcription Factor ◽  
Hair Cells ◽  
Mirror Image ◽  
Hair Bundle ◽  
Polarity Reversal ◽  
Lateral Line System ◽  
Apical Surface ◽  
Sensory Organs ◽  
Line System ◽  
Image Pattern

The asymmetric location of stereociliary bundle (hair bundle) on the apical surface of mechanosensory hair cells (HCs) dictates the direction in which a given HC can respond to cues such as sound, head movements, and water pressure. Notably, vestibular sensory organs of the inner ear, the maculae, exhibit a line of polarity reversal (LPR) across which, hair bundles are polarized in a mirror-image pattern. Similarly, HCs in neuromasts of the zebrafish lateral line system are generated as pairs, and two sibling HCs develop opposite hair bundle orientations. Within these sensory organs, expression of the transcription factor Emx2 is restricted to only one side of the LPR in the maculae or one of the two sibling HCs in neuromasts. Emx2 mediates hair bundle polarity reversal in these restricted subsets of HCs and generates the mirror-image pattern of the sensory organs. Downstream effectors of Emx2 control bundle polarity cell-autonomously via heterotrimeric G proteins.

scholarly journals Direct mechanical stimulation of tip links in hair cells through DNA tethers

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Aakash Basu ◽  
Samuel Lagier ◽  
Maria Vologodskaia ◽  
Brian A Fabella ◽  
AJ Hudspeth
Keyword(s):  
Magnetic Field ◽  
Field Gradient ◽  
Mechanical Stimulation ◽  
Hair Cells ◽  
Magnetic Field Gradient ◽  
Hair Bundle ◽  
Mechanical Forces ◽  
Mechanoelectrical Transduction ◽  
Superparamagnetic Beads ◽  
Stimulation Of

Mechanoelectrical transduction by hair cells commences with hair-bundle deflection, which is postulated to tense filamentous tip links connected to transduction channels. Because direct mechanical stimulation of tip links has not been experimentally possible, this hypothesis has not been tested. We have engineered DNA tethers that link superparamagnetic beads to tip links and exert mechanical forces on the links when exposed to a magnetic-field gradient. By pulling directly on tip links of the bullfrog's sacculus we have evoked transduction currents from hair cells, confirming the hypothesis that tension in the tip links opens transduction channels. This demonstration of direct mechanical access to tip links additionally lays a foundation for experiments probing the mechanics of individual channels.

scholarly journals Connectomics of the zebrafish's lateral-line neuromast reveals wiring and miswiring in a simple microcircuit

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Eliot Dow ◽  
Adrian Jacobo ◽  
Sajjad Hossain ◽  
Kimberly Siletti ◽  
A J Hudspeth
Keyword(s):  
Hair Cell ◽  
Lateral Line ◽  
Hair Cells ◽  
Planar Cell Polarity ◽  
Developmental Stages ◽  
Notch Signaling Pathway ◽  
Nerve Fibers ◽  
Directional Sensitivity ◽  
Efferent Nerve ◽  
Polarity Gene

The lateral-line neuromast of the zebrafish displays a restricted, consistent pattern of innervation that facilitates the comparison of microcircuits across individuals, developmental stages, and genotypes. We used serial blockface scanning electron microscopy to determine from multiple specimens the neuromast connectome, a comprehensive set of connections between hair cells and afferent and efferent nerve fibers. This analysis delineated a complex but consistent wiring pattern with three striking characteristics: each nerve terminal is highly specific in receiving innervation from hair cells of a single directional sensitivity; the innervation is redundant; and the terminals manifest a hierarchy of dominance. Mutation of the canonical planar-cell-polarity gene vangl2, which decouples the asymmetric phenotypes of sibling hair-cell pairs, results in randomly positioned, randomly oriented sibling cells that nonetheless retain specific wiring. Because larvae that overexpress Notch exhibit uniformly oriented, uniformly innervating hair-cell siblings, wiring specificity is mediated by the Notch signaling pathway.

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