1. Cell Biology
  2. Developmental Biology
Download icon

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
Research Advance
  • Cited 0
  • Views 671
  • Annotations
Cite this article as: eLife 2020;9:e59282 doi: 10.7554/eLife.59282

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).

Reviewing Editor

  1. Tanya T Whitfield, University of Sheffield, United Kingdom

Publication history

  1. Received: May 28, 2020
  2. Accepted: September 17, 2020
  3. Accepted Manuscript published: September 23, 2020 (version 1)
  4. Version of Record published: October 5, 2020 (version 2)

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

  • 671
    Page views
  • 123
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

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

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

Further reading

    1. Cell Biology
    Guangfeng Geng et al.
    Research Article Updated

    Erythropoietin (EPO) drives erythropoiesis and is secreted mainly by the kidney upon hypoxic or anemic stress. The paucity of EPO production in renal EPO-producing cells (REPs) causes renal anemia, one of the most common complications of chronic nephropathies. Although mitochondrial dysfunction is commonly observed in several renal and hematopoietic disorders, the mechanism by which mitochondrial quality control impacts renal anemia remains elusive. In this study, we showed that FUNDC1, a mitophagy receptor, plays a critical role in EPO-driven erythropoiesis induced by stresses. Mechanistically, EPO production is impaired in REPs in Fundc1-/- mice upon stresses, and the impairment is caused by the accumulation of damaged mitochondria, which consequently leads to the elevation of the reactive oxygen species (ROS) level and triggers inflammatory responses by up-regulating proinflammatory cytokines. These inflammatory factors promote the myofibroblastic transformation of REPs, resulting in the reduction of EPO production. We therefore provide a link between aberrant mitophagy and deficient EPO generation in renal anemia. Our results also suggest that the mitochondrial quality control safeguards REPs under stresses, which may serve as a potential therapeutic strategy for the treatment of renal anemia.

    1. Cell Biology
    2. Chromosomes and Gene Expression
    Yu-Xuan Lu et al.
    Research Article

    Age-related changes to histone levels are seen in many species. However, it is unclear whether changes to histone expression could be exploited to ameliorate the effects of ageing in multicellular organisms. Here we show that inhibition of mTORC1 by the lifespan-extending drug rapamycin increases expression of histones H3 and H4 post-transcriptionally, through eIF3-mediated translation. Elevated expression of H3/H4 in intestinal enterocytes in Drosophila alters chromatin organization, induces intestinal autophagy through transcriptional regulation, prevents age-related decline in the intestine. Importantly, it also mediates rapamycin-induced longevity and intestinal health. Histones H3/H4 regulate expression of an autophagy cargo adaptor Bchs (WDFY3 in mammals), increased expression of which in enterocytes mediates increased H3/H4-dependent healthy longevity. In mice, rapamycin treatment increases expression of histone proteins and Wdfy3 transcription, and alters chromatin organisation in the small intestine, suggesting the mTORC1-histone axis is at least partially conserved in mammals and may offer new targets for anti-ageing interventions.