From local resynchronization to global pattern recovery in the zebrafish segmentation clock

  1. Koichiro Uriu  Is a corresponding author
  2. Bo-Kai Liao
  3. Andrew C Oates
  4. Luis G Morelli
  1. Kanazawa University, Japan
  2. National Taiwan Ocean University, Taiwan
  3. École polytechnique fédérale de Lausanne, Switzerland
  4. Instituto de Investigación en Biomedicina de Buenos Aires, Argentina

Abstract

Integrity of rhythmic spatial gene expression patterns in the vertebrate segmentation clock requires local synchronization between neighboring cells by Delta-Notch signaling and its inhibition causes defective segment boundaries. Whether deformation of the oscillating tissue complements local synchronization during patterning and segment formation is not understood. We combine theory and experiment to investigate this question in the zebrafish segmentation clock. We remove a Notch inhibitor, allowing resynchronization, and analyze embryonic segment recovery. We observe unexpected intermingling of normal and defective segments, and capture this with a new model combining coupled oscillators and tissue mechanics. Intermingled segments are explained in the theory by advection of persistent phase vortices of oscillators. Experimentally observed changes in recovery patterns are predicted in the theory by temporal changes in tissue length and cell advection pattern. Thus, segmental pattern recovery occurs at two length and time scales: rapid local synchronization between neighboring cells, and the slower transport of the resulting patterns across the tissue through morphogenesis.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Koichiro Uriu

    Natural Science and Technology, Kanazawa University, Kanazawa, Japan
    For correspondence
    uriu@staff.kanazawa-u.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1802-2470
  2. Bo-Kai Liao

    Department of Aquaculture, National Taiwan Ocean University, Keelung, Taiwan
    Competing interests
    The authors declare that no competing interests exist.
  3. Andrew C Oates

    École polytechnique fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3015-3978
  4. Luis G Morelli

    Cellular Plasticity, Instituto de Investigación en Biomedicina de Buenos Aires, Buenos Aires, Argentina
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5614-073X

Funding

Japan Society for the Promotion of Science (KAKENHI grant number 17H05762)

  • Koichiro Uriu

ANPCyT (PICT 2013 1301)

  • Luis G Morelli

ANPCyT (PICT 2017 3753)

  • Luis G Morelli

FOCEM-Mercosur (COF 03/11)

  • Luis G Morelli

Japan Society for the Promotion of Science (Short Term Grant S17064)

  • Koichiro Uriu
  • Luis G Morelli

Japan Society for the Promotion of Science (KAKENHI grant number 19H04955)

  • Koichiro Uriu

Japan Society for the Promotion of Science (KAKENHI grant number 19H04772)

  • Koichiro Uriu

Ministry of Science and Technology, Taiwan (MOST 108-2311-B-019-001-MY3)

  • Bo-Kai Liao

SNSF Project funding division III (31003A_176037)

  • Andrew C Oates

Wellcome Trust Senior Research Fellowship in Basic Biomedical Science (WT098025MA)

  • Andrew C Oates

European Research Council Starting Independent Research Grant (ERC-2007-StG: 207634)

  • Bo-Kai Liao
  • Andrew C Oates

Francis Crick Institute

  • Bo-Kai Liao
  • Andrew C Oates

ANPCyT (PICT 2012 1954)

  • Luis G Morelli

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

Ethics

Animal experimentation: Zebrafish experimentation was carried out in strict accordance with the ethics and regulations of the Saxonian Ministry of the Environment and Agriculture in Germany under licence Az. 74-9165.40-9-2001, and the Home Office in the United Kingdom under project licence PPL No. 70/7675.

Copyright

© 2021, Uriu 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

  • 1,537
    views

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

Download links

Share this article

https://doi.org/10.7554/eLife.61358

Further reading

    1. Developmental Biology
    Hanee Lee, Junsu Kang ... Junho Lee
    Research Article

    The evolutionarily conserved Hippo (Hpo) pathway has been shown to impact early development and tumorigenesis by governing cell proliferation and apoptosis. However, its post-developmental roles are relatively unexplored. Here, we demonstrate its roles in post-mitotic cells by showing that defective Hpo signaling accelerates age-associated structural and functional decline of neurons in Caenorhabditis elegans. Loss of wts-1/LATS, the core kinase of the Hpo pathway, resulted in premature deformation of touch neurons and impaired touch responses in a yap-1/YAP-dependent manner, the downstream transcriptional co-activator of LATS. Decreased movement as well as microtubule destabilization by treatment with colchicine or disruption of microtubule-stabilizing genes alleviated the neuronal deformation of wts-1 mutants. Colchicine exerted neuroprotective effects even during normal aging. In addition, the deficiency of a microtubule-severing enzyme spas-1 also led to precocious structural deformation. These results consistently suggest that hyper-stabilized microtubules in both wts-1-deficient neurons and normally aged neurons are detrimental to the maintenance of neuronal structural integrity. In summary, Hpo pathway governs the structural and functional maintenance of differentiated neurons by modulating microtubule stability, raising the possibility that the microtubule stability of fully developed neurons could be a promising target to delay neuronal aging. Our study provides potential therapeutic approaches to combat age- or disease-related neurodegeneration.

    1. Developmental Biology
    Alexandra V Bruter, Ekaterina A Varlamova ... Victor V Tatarskiy
    Research Article

    CDK8 and CDK19 paralogs are regulatory kinases associated with the transcriptional Mediator complex. We have generated mice with the systemic inducible Cdk8 knockout on the background of Cdk19 constitutive knockout. Cdk8/19 double knockout (iDKO) males, but not single Cdk8 or Cdk19 KO, had an atrophic reproductive system and were infertile. The iDKO males lacked postmeiotic spermatids and spermatocytes after meiosis I pachytene. Testosterone levels were decreased whereas the amounts of the luteinizing hormone were unchanged. Single-cell RNA sequencing showed marked differences in the expression of steroidogenic genes (such as Cyp17a1, Star, and Fads) in Leydig cells concomitant with alterations in Sertoli cells and spermatocytes, and were likely associated with an impaired synthesis of steroids. Star and Fads were also downregulated in cultured Leydig cells after iDKO. The treatment of primary Leydig cell culture with a CDK8/19 inhibitor did not induce the same changes in gene expression as iDKO, and a prolonged treatment of mice with a CDK8/19 inhibitor did not affect the size of testes. iDKO, in contrast to the single knockouts or treatment with a CDK8/19 kinase inhibitor, led to depletion of cyclin C (CCNC), the binding partner of CDK8/19 that has been implicated in CDK8/19-independent functions. This suggests that the observed phenotype was likely mediated through kinase-independent activities of CDK8/19, such as CCNC stabilization.