1. Developmental Biology
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Notch/Her12 signalling modulates motile/immotile cilia ratio downstream of Foxj1a in zebrafish left-right organizer

  1. Barbara Tavares
  2. Raquel Jacinto
  3. Pedro Sampaio
  4. Sara Pestana
  5. Andreia Pinto
  6. Andreia Vaz
  7. Mónica Roxo-Rosa
  8. Rui Gardner
  9. Telma Lopes
  10. Britta Schilling
  11. Ian Henry
  12. Leonor Saúde
  13. Susana Santos Lopes  Is a corresponding author
  1. CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Universidade Nova de Lisboa, Portugal
  2. Instituto de Medicina Molecular, Centro Académico de Medicina de Lisboa, Portugal
  3. Instituto Gulbenkian de Ciencia, Portugal
  4. Max Planck Institute of Molecular Cell Biology and Genetics, Germany
  5. Instituto de Medicina Molecular, Portugal
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Cite this article as: eLife 2017;6:e25165 doi: 10.7554/eLife.25165

Abstract

Foxj1a is necessary and sufficient to specify motile cilia. Using transcriptional studies and slow-scan two-photon live imaging capable of identifying the number of motile and immotile cilia, we now established that the final number of motile cilia depends on Notch signalling (NS). We found that despite all left-right organizer (LRO) cells express foxj1a and the ciliary axonemes of these cells have dynein arms some cilia remain immotile. We identified that this decision is taken early in development in the Kupffer’s Vesicle (KV) precursors the readout being her12 transcription. We demonstrate that overexpression of either her12 or Notch intracellular domain (NICD) increases the number of immotile cilia at the expense of motile cilia, and leads to an accumulation of immotile cilia at the anterior half of the KV. This disrupts the normal fluid flow intensity and pattern, with consequent impact on dand5 expression pattern and left-right (L-R) axis establishment.

Article and author information

Author details

  1. Barbara Tavares

    Faculdade de Ciências Médicas, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  2. Raquel Jacinto

    Faculdade de Ciências Médicas, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4029-0204
  3. Pedro Sampaio

    Faculdade de Ciências Médicas, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  4. Sara Pestana

    Faculdade de Ciências Médicas, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  5. Andreia Pinto

    Laboratório de Histologia e Patologia Comparada, Instituto de Medicina Molecular, Centro Académico de Medicina de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  6. Andreia Vaz

    Faculdade de Ciências Médicas, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  7. Mónica Roxo-Rosa

    Faculdade de Ciências Médicas, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  8. Rui Gardner

    Instituto Gulbenkian de Ciencia, Oeiras, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  9. Telma Lopes

    Instituto Gulbenkian de Ciencia, Oeiras, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  10. Britta Schilling

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Ian Henry

    Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
  12. Leonor Saúde

    Faculdade de Medicina de Lisboa, Instituto de Medicina Molecular, Lisbon, Portugal
    Competing interests
    The authors declare that no competing interests exist.
  13. Susana Santos Lopes

    Faculdade de Ciências Médicas, CEDOC, Chronic Diseases Research Centre, NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal
    For correspondence
    susana.lopes@fcm.unl.pt
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6733-6356

Funding

Fundação para a Ciência e a Tecnologia (PTDC/BEX-BID/1411/2014)

  • Susana Santos Lopes

Fundação para a Ciência e a Tecnologia (FCT-ANR/BEX-BID/0153/2012)

  • Sara Pestana

Fundação para a Ciência e a Tecnologia (PTDC/SAU-OBD/103981/2008)

  • Andreia Vaz

Fundação para a Ciência e a Tecnologia (PD/BD/52420/2013)

  • Raquel Jacinto

Fundação para a Ciência e a Tecnologia (SFRH/BPD/77258/2011)

  • Barbara Tavares

Fundação para a Ciência e a Tecnologia (SFRH/BD/111611/2015)

  • Pedro Sampaio

Fundação para a Ciência e a Tecnologia (IF/00951/2012)

  • Susana Santos Lopes

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

Reviewing Editor

  1. Jeremy F Reiter, University of California, San Francisco, United States

Publication history

  1. Received: January 16, 2017
  2. Accepted: September 3, 2017
  3. Accepted Manuscript published: September 6, 2017 (version 1)
  4. Version of Record published: September 21, 2017 (version 2)

Copyright

© 2017, Tavares 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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