1. Developmental Biology
  2. Neuroscience
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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
Research Article
  • Cited 31
  • Views 3,806
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Cite this article as: eLife 2017;6:e23661 doi: 10.7554/eLife.23661

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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Further reading

    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.

    1. Chromosomes and Gene Expression
    2. Developmental Biology
    Rozenn Riou et al.
    Research Article

    Erythropoietin (EPO) is a key regulator of erythropoiesis. The embryonic liver is the main site of erythropoietin synthesis, after which the kidney takes over. The adult liver retains the ability to express EPO, and we discovered here new players of this transcription, distinct from the classical hypoxia-inducible factor pathway. In mice genetically-invalidated in hepatocytes for the chromatin remodeler Arid1a, and for Apc, the major silencer of Wnt pathway, chromatin was more accessible and histone marks turned into active ones at the Epo downstream enhancer. Activating β-catenin signaling increased binding of Tcf4/β-catenin complex and upregulated its enhancer function. The loss of Arid1a together with β-catenin signaling, resulted in cell-autonomous EPO transcription in mouse and human hepatocytes. In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. Thus, we identified new hepatic EPO regulation mechanism stimulating erythropoiesis.