Distribution of neurosensory progenitor pools during inner ear morphogenesis unveiled by cell lineage reconstruction

  1. Sylvia Dyballa
  2. Thierry Savy
  3. Philipp Germann
  4. Karol Mikula
  5. Mariana Remesikova
  6. Róbert Špir
  7. Andrea Zecca
  8. Nadine Peyriéras
  9. Cristina Pujades  Is a corresponding author
  1. Universitat Pompeu Fabra, Spain
  2. USR3695 CNRS, France
  3. Center for Genomic Regulation, Spain
  4. Slovak University of Technology, Slovakia

Abstract

Reconstructing the lineage of cells is central to understanding how the wide diversity of cell types develops. Here, we provide the neurosensory lineage reconstruction of a complex sensory organ, the inner ear, by imaging zebrafish embryos in vivo over an extended timespan, combining cell tracing and cell fate marker expression over time. We deliver the first dynamic map of early neuronal and sensory progenitor pools in the whole otic vesicle. It highlights the remodeling of the neuronal progenitor domain upon neuroblast delamination, and reveals that the order and place of neuroblasts' delamination from the otic epithelium prefigure their position within the SAG. Sensory and non-sensory domains harbor different proliferative activity contributing distinctly to the overall growth of the structure. Therefore, the otic vesicle case exemplifies a generic morphogenetic process where spatial and temporal cues regulate cell fate and functional organization of the rudiment of the definitive organ.

Article and author information

Author details

  1. Sylvia Dyballa

    Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  2. Thierry Savy

    Multilevel Dynamics in Morphogenesis Unit, USR3695 CNRS, Gif sur Yvette, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Philipp Germann

    Systems Biology Unit, Center for Genomic Regulation, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2057-4883
  4. Karol Mikula

    Department of Mathematics, Slovak University of Technology, Bratislava, Slovakia
    Competing interests
    The authors declare that no competing interests exist.
  5. Mariana Remesikova

    Department of Mathematics, Slovak University of Technology, Bratislava, Slovakia
    Competing interests
    The authors declare that no competing interests exist.
  6. Róbert Špir

    Department of Mathematics, Slovak University of Technology, Bratislava, Slovakia
    Competing interests
    The authors declare that no competing interests exist.
  7. Andrea Zecca

    Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  8. Nadine Peyriéras

    Multilevel Dynamics in Morphogenesis Unit, USR3695 CNRS, Gif sur Yvette, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Cristina Pujades

    Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
    For correspondence
    cristina.pujades@upf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6423-7451

Funding

Ministerio de Economía y Competitividad (BFU2012-31994)

  • Cristina Pujades

Agence Nationale de la Recherche (ANR-10-INBS-04)

  • Cristina Pujades

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CRSII3 141918)

  • Philipp Germann

Ministerio de Economía y Competitividad (MDM-2014-0370)

  • Cristina Pujades

Ministerio de Economía y Competitividad (SEV-2012-0208)

  • Philipp Germann

Agence Nationale de la Recherche (ANR-11-EQPX-0029)

  • Thierry Savy

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

Reviewing Editor

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

Ethics

Animal experimentation: This study was performed in strict accordance with the European Regulations. Zebrafish embryos were obtained by mating of adult fish using standard methods. All fish strains were maintained individually as inbred lines. All protocols used have been approved by the Institutional Animal Care and Use Ethic Committee (PRBB-IACUEC), and implemented according to national and European regulations. All experiments were carried out in accordance with the principles of the 3Rs. All our experiments were carried out using the CPC16-008/9125 protocol approved by the Generalitat of Catalonia.

Version history

  1. Received: October 11, 2016
  2. Accepted: December 23, 2016
  3. Accepted Manuscript published: January 4, 2017 (version 1)
  4. Accepted Manuscript updated: January 12, 2017 (version 2)
  5. Version of Record published: January 18, 2017 (version 3)

Copyright

© 2017, Dyballa 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.

Metrics

  • 1,743
    views
  • 396
    downloads
  • 20
    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. Sylvia Dyballa
  2. Thierry Savy
  3. Philipp Germann
  4. Karol Mikula
  5. Mariana Remesikova
  6. Róbert Špir
  7. Andrea Zecca
  8. Nadine Peyriéras
  9. Cristina Pujades
(2017)
Distribution of neurosensory progenitor pools during inner ear morphogenesis unveiled by cell lineage reconstruction
eLife 6:e22268.
https://doi.org/10.7554/eLife.22268

Share this article

https://doi.org/10.7554/eLife.22268

Further reading

    1. Cancer Biology
    2. Cell Biology
    Camille Dantzer, Justine Vaché ... Violaine Moreau
    Research Article

    Immune checkpoint inhibitors have produced encouraging results in cancer patients. However, the majority of ß-catenin-mutated tumors have been described as lacking immune infiltrates and resistant to immunotherapy. The mechanisms by which oncogenic ß-catenin affects immune surveillance remain unclear. Herein, we highlighted the involvement of ß-catenin in the regulation of the exosomal pathway and, by extension, in immune/cancer cell communication in hepatocellular carcinoma (HCC). We showed that mutated ß-catenin represses expression of SDC4 and RAB27A, two main actors in exosome biogenesis, in both liver cancer cell lines and HCC patient samples. Using nanoparticle tracking analysis and live-cell imaging, we further demonstrated that activated ß-catenin represses exosome release. Then, we demonstrated in 3D spheroid models that activation of β-catenin promotes a decrease in immune cell infiltration through a defect in exosome secretion. Taken together, our results provide the first evidence that oncogenic ß-catenin plays a key role in exosome biogenesis. Our study gives new insight into the impact of ß-catenin mutations on tumor microenvironment remodeling, which could lead to the development of new strategies to enhance immunotherapeutic response.

    1. Cell Biology
    Zhongyun Xie, Yongping Chai ... Wei Li
    Research Article

    Asymmetric cell divisions (ACDs) generate two daughter cells with identical genetic information but distinct cell fates through epigenetic mechanisms. However, the process of partitioning different epigenetic information into daughter cells remains unclear. Here, we demonstrate that the nucleosome remodeling and deacetylase (NuRD) complex is asymmetrically segregated into the surviving daughter cell rather than the apoptotic one during ACDs in Caenorhabditis elegans. The absence of NuRD triggers apoptosis via the EGL-1-CED-9-CED-4-CED-3 pathway, while an ectopic gain of NuRD enables apoptotic daughter cells to survive. We identify the vacuolar H+–adenosine triphosphatase (V-ATPase) complex as a crucial regulator of NuRD’s asymmetric segregation. V-ATPase interacts with NuRD and is asymmetrically segregated into the surviving daughter cell. Inhibition of V-ATPase disrupts cytosolic pH asymmetry and NuRD asymmetry. We suggest that asymmetric segregation of V-ATPase may cause distinct acidification levels in the two daughter cells, enabling asymmetric epigenetic inheritance that specifies their respective life-versus-death fates.