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

Unidad de Excelencia María de Maetzu (2015-19 MDM-2014-0370 to DCEXS-UPF)

  • Sylvia Dyballa
  • Andrea Zecca
  • Cristina Pujades

Centro de Excelencia Severo Ochoa (2013-17 SEV-2012-0208 to CRG)

  • Philipp Germann

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

  • Nadine Peyriéras

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

  • Nadine Peyriéras

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SINERGIA CRSII3 141918)

  • Philipp Germann

Becas de la Generalitat de Catalunya (Predoctoral FI-fellowship)

  • Sylvia Dyballa
  • Andrea Zecca

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
    Mengya Zhao, Beiying Dai ... Yijun Chen
    Research Article

    Philadelphia chromosome-positive (Ph+) leukemia is a fatal hematological malignancy. Although standard treatments with tyrosine kinase inhibitors (TKIs) have achieved remarkable success in prolonging patient survival, intolerance, relapse, and TKI resistance remain serious issues for patients with Ph+ leukemia. Here, we report a new leukemogenic process in which RAPSYN and BCR-ABL co-occur in Ph+ leukemia, and RAPSYN mediates the neddylation of BCR-ABL. Consequently, neddylated BCR-ABL enhances the stability by competing its c-CBL-mediated degradation. Furthermore, SRC phosphorylates RAPSYN to activate its NEDD8 E3 ligase activity, promoting BCR-ABL stabilization and disease progression. Moreover, in contrast to in vivo ineffectiveness of PROTAC-based degraders, depletion of RAPSYN expression, or its ligase activity decreased BCR-ABL stability and, in turn, inhibited tumor formation and growth. Collectively, these findings represent an alternative to tyrosine kinase activity for the oncoprotein and leukemogenic cells and generate a rationale of targeting RAPSYN-mediated BCR-ABL neddylation for the treatment of Ph+ leukemia.

    1. Cell Biology
    2. Genetics and Genomics
    Yangzi Zhao, Lijun Ren ... Zhukuan Cheng
    Research Article

    Cohesin is a multi-subunit protein that plays a pivotal role in holding sister chromatids together during cell division. Sister chromatid cohesion 3 (SCC3), constituents of cohesin complex, is highly conserved from yeast to mammals. Since the deletion of individual cohesin subunit always causes lethality, it is difficult to dissect its biological function in both mitosis and meiosis. Here, we obtained scc3 weak mutants using CRISPR-Cas9 system to explore its function during rice mitosis and meiosis. The scc3 weak mutants displayed obvious vegetative defects and complete sterility, underscoring the essential roles of SCC3 in both mitosis and meiosis. SCC3 is localized on chromatin from interphase to prometaphase in mitosis. However, in meiosis, SCC3 acts as an axial element during early prophase I and subsequently situates onto centromeric regions following the disassembly of the synaptonemal complex. The loading of SCC3 onto meiotic chromosomes depends on REC8. scc3 shows severe defects in homologous pairing and synapsis. Consequently, SCC3 functions as an axial element that is essential for maintaining homologous chromosome pairing and synapsis during meiosis.