Transcription factor Emx2 controls stereociliary bundle orientation of sensory hair cells

  1. Tao Jiang
  2. Katie Kindt  Is a corresponding author
  3. Doris K Wu  Is a corresponding author
  1. University of Maryland, United States
  2. National Institutes of Health, United States

Abstract

The asymmetric location of stereociliary bundle (hair bundle) on 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.

Article and author information

Author details

  1. Tao Jiang

    Program in Neuroscience and Cognitive Science, University of Maryland, College Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Katie Kindt

    Section on Sensory Cell Development, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States
    For correspondence
    katie.kindt@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1065-8215
  3. Doris K Wu

    Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States
    For correspondence
    wud@nidcd.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1400-3558

Funding

National Institutes of Health

  • Doris K Wu

National Institutes of Health

  • Katie Kindt

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments were conducted under approved NIH animal protocols (#1212-14, #1362-13) and according to NIH animal user guidelines.

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: November 26, 2016
  2. Accepted: March 4, 2017
  3. Accepted Manuscript published: March 7, 2017 (version 1)
  4. Accepted Manuscript updated: March 8, 2017 (version 2)
  5. Version of Record published: April 11, 2017 (version 3)

Copyright

© 2017, Jiang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Tao Jiang
  2. Katie Kindt
  3. Doris K Wu
(2017)
Transcription factor Emx2 controls stereociliary bundle orientation of sensory hair cells
eLife 6:e23661.
https://doi.org/10.7554/eLife.23661

Further reading

    1. Cell Biology
    2. Developmental Biology
    Yosuke Tona, Doris K Wu
    Research Advance Updated

    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.

    1. Developmental Biology
    2. Neuroscience
    Young Rae Ji et al.
    Research Advance Updated

    The orientation of hair bundles on top of sensory hair cells (HCs) in neuromasts of the lateral line system allows fish to detect direction of water flow. Each neuromast shows hair bundles arranged in two opposing directions and each afferent neuron innervates only HCs of the same orientation. Previously, we showed that this opposition is established by expression of Emx2 in half of the HCs, where it mediates hair bundle reversal (Jiang et al., 2017). Here, we show that Emx2 also regulates neuronal selection: afferent neurons innervate either Emx2-positive or negative HCs. In emx2 knockout and gain-of-function neuromasts, all HCs are unidirectional and the innervation patterns and physiological responses of the afferent neurons are dependent on the presence or absence of Emx2. Our results indicate that Emx2 mediates the directional selectivity of neuromasts by two distinct processes: regulating hair bundle orientation in HCs and selecting afferent neuronal targets.