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

  1. Yosuke Tona
  2. Doris K Wu  Is a corresponding author
  1. NIDCD, NIH, United States

Abstract

The asymmetric hair bundle on top of hair cells (HCs), comprises a kinocilium and stereocilia staircase, dictates HC's 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.

Data availability

The following figures contain the source data files. Figure 2 (source data 1), Figure 2 supplement 2 (source data 1-3), Figure 2 supplement 3 (source data 1-4), Figure 2 supplement 4 (source data 1-2), Figure 3 (source data 1-2), figure 3 supplement 2 (source data 1), Figure 4 (source data 1-2), Figure 5 (source data 1), Figure 6 (source data 1-2), Figure 7 (source data 1), Figure 7 supplement 1 (source data 1), Figure 8 (source data 1-2), Figure 9 (source data 1).

Article and author information

Author details

  1. Yosuke Tona

    Section on Sensory Cell Regeneration and Development, Laboratory of Molecular Biology, NIDCD, NIH, Bethesda, United States
    Competing interests
    No competing interests declared.
  2. Doris K Wu

    Section on Sensory Cell Regeneration and Development, Laboratory of Molecular Biology, NIDCD, NIH, Bethesda, United States
    For correspondence
    wud@nidcd.nih.gov
    Competing interests
    Doris K Wu, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1400-3558

Funding

National Institutes of Health (1ZIADC000021)

  • Yosuke Tona

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 according to NIH guidelines and under the approved Animal Care Protocol of NIDCD/NIH (#1212-17).

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 1,807
    views
  • 195
    downloads
  • 13
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Yosuke Tona
  2. Doris K Wu
(2020)
Live imaging of hair bundle polarity acquisition demonstrates a critical timeline for transcription factor Emx2
eLife 9:e59282.
https://doi.org/10.7554/eLife.59282

Share this article

https://doi.org/10.7554/eLife.59282

Further reading

    1. Cell Biology
    2. Developmental Biology
    Jeet H Patel, Mary C Mullins
    Insight

    Disease-causing mutations in the signaling protein BMP4 impair its secretion, but only when it is made as a homodimer.

    1. Cell Biology
    2. Medicine
    Shuo He, Lei Huang ... Jinlong He
    Research Article

    Disturbed shear stress-induced endothelial atherogenic responses are pivotal in the initiation and progression of atherosclerosis, contributing to the uneven distribution of atherosclerotic lesions. This study investigates the role of Aff3ir-ORF2, a novel nested gene variant, in disturbed flow-induced endothelial cell activation and atherosclerosis. We demonstrate that disturbed shear stress significantly reduces Aff3ir-ORF2 expression in athero-prone regions. Using three distinct mouse models with manipulated Aff3ir-ORF2 expression, we demonstrate that Aff3ir-ORF2 exerts potent anti-inflammatory and anti-atherosclerotic effects in Apoe-/- mice. RNA sequencing revealed that interferon regulatory factor 5 (Irf5), a key regulator of inflammatory processes, mediates inflammatory responses associated with Aff3ir-ORF2 deficiency. Aff3ir-ORF2 interacts with Irf5, promoting its retention in the cytoplasm, thereby inhibiting the Irf5-dependent inflammatory pathways. Notably, Irf5 knockdown in Aff3ir-ORF2 deficient mice almost completely rescues the aggravated atherosclerotic phenotype. Moreover, endothelial-specific Aff3ir-ORF2 supplementation using the CRISPR/Cas9 system significantly ameliorated endothelial activation and atherosclerosis. These findings elucidate a novel role for Aff3ir-ORF2 in mitigating endothelial inflammation and atherosclerosis by acting as an inhibitor of Irf5, highlighting its potential as a valuable therapeutic approach for treating atherosclerosis.