1. Developmental Biology
Download icon

Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism

  1. Eduardo Pulgar
  2. Cornelia Schwayer
  3. Néstor Guerrero
  4. Loreto López
  5. Susana Márquez
  6. Steffen Härtel
  7. Rodrigo Soto
  8. Carl-Philipp Heisenberg
  9. Miguel Concha  Is a corresponding author
  1. Universidad de Chile, Chile
  2. Institute of Science and Technology Austria (IST Austria), Austria
  3. Institute of Science and Technology Austria, Austria
Research Article
  • Cited 0
  • Views 615
  • Annotations
Cite this article as: eLife 2021;10:e66483 doi: 10.7554/eLife.66483

Abstract

The developmental strategies used by progenitor cells to allow a safe journey from their induction place towards the site of terminal differentiation are still poorly understood. Here we uncovered a mechanism of progenitor cell allocation that stems from an incomplete process of epithelial delamination that allows progenitors to coordinate their movement with adjacent extra-embryonic tissues. Progenitors of the zebrafish laterality organ originate from the superficial epithelial enveloping layer by an apical constriction process of cell delamination. During this process, progenitors retain long-lasting apical contacts that enable the epithelial layer to pull a subset of progenitors on their way to the vegetal pole. The remaining delaminated cells follow the movement of apically attached progenitors by a protrusion-dependent cell-cell contact mechanism, avoiding sequestration by the adjacent endoderm, ensuring their collective fate and allocation at the site of differentiation. Thus, we reveal that incomplete delamination serves as a cellular platform for coordinated tissue movements during development.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1, 2, 3, 4, 5, 6, 7 and 8.

Article and author information

Author details

  1. Eduardo Pulgar

    Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
    Competing interests
    The authors declare that no competing interests exist.
  2. Cornelia Schwayer

    no Department, Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
  3. Néstor Guerrero

    Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
    Competing interests
    The authors declare that no competing interests exist.
  4. Loreto López

    Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
    Competing interests
    The authors declare that no competing interests exist.
  5. Susana Márquez

    Physics Department, FCFM, Universidad de Chile, Santiago, Chile
    Competing interests
    The authors declare that no competing interests exist.
  6. Steffen Härtel

    Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
    Competing interests
    The authors declare that no competing interests exist.
  7. Rodrigo Soto

    Physics Department, FCFM, Universidad de Chile, Santiago, Chile
    Competing interests
    The authors declare that no competing interests exist.
  8. Carl-Philipp Heisenberg

    Life Sciences, Institute of Science and Technology Austria, Klosterneuburg, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0912-4566
  9. Miguel Concha

    Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
    For correspondence
    miguelconcha@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3353-9398

Funding

Fondo Nacional de Desarrollo Científico y Tecnológico (1190806)

  • Eduardo Pulgar
  • Steffen Härtel
  • Miguel Concha

Comisión Nacional de Investigación Científica y Tecnológica (REDES170212,REDES130020)

  • Eduardo Pulgar
  • Steffen Härtel
  • Miguel Concha

H2020 European Research Council (Advanced grant 742573)

  • Carl-Philipp Heisenberg

Fondo Nacional de Desarrollo Científico y Tecnológico (1161274,1181823)

  • Steffen Härtel
  • Miguel Concha

Instituto Milenio de Neurociencia Biomedica (ICN09_015)

  • Eduardo Pulgar
  • Steffen Härtel
  • Miguel Concha

Millennium Nucleus Physics of Active Matter from ANID (ANID)

  • Susana Márquez
  • Rodrigo Soto
  • Miguel Concha

Fondo de Equipamiento Cientifico y Tecnologico (EQM130051)

  • Steffen Härtel
  • Miguel Concha

Fondo de Financiamiento de Centros de Investigacion en Areas Prioritarias (15150012)

  • Miguel Concha

Fondo Nacional de Desarrollo Científico y Tecnológico (3160478)

  • Eduardo Pulgar

Comisión Nacional de Investigación Científica y Tecnológica (PIA ACT-1402)

  • Steffen Härtel
  • Miguel Concha

Comisión Nacional de Investigación Científica y Tecnológica (PIA ACT192015)

  • Miguel Concha

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

Ethics

Animal experimentation: Fish care and procedures were approved by the Ethical Review Committee and comply with the Animals Scientific Procedures Act 0466 (Protocol CBA#0466 FMUCH).

Reviewing Editor

  1. Julien Vermot

Publication history

  1. Received: January 12, 2021
  2. Preprint posted: April 29, 2021 (view preprint)
  3. Accepted: August 25, 2021
  4. Accepted Manuscript published: August 27, 2021 (version 1)
  5. Version of Record published: September 23, 2021 (version 2)

Copyright

© 2021, Pulgar 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

  • 615
    Page views
  • 107
    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. Chromosomes and Gene Expression
    2. Developmental Biology
    Benoit Roch et al.
    Research Article Updated

    We developed an Xrcc4M61R separation of function mouse line to overcome the embryonic lethality of Xrcc4-deficient mice. XRCC4M61R protein does not interact with Xlf, thus obliterating XRCC4-Xlf filament formation while preserving the ability to stabilize DNA ligase IV. X4M61R mice, which are DNA repair deficient, phenocopy the Nhej1-/- (known as Xlf -/-) setting with a minor impact on the development of the adaptive immune system. The core non-homologous end-joining (NHEJ) DNA repair factor XRCC4 is therefore not mandatory for V(D)J recombination aside from its role in stabilizing DNA ligase IV. In contrast, Xrcc4M61R mice crossed on Paxx-/-, Nhej1-/-, or Atm-/- backgrounds are severely immunocompromised, owing to aborted V(D)J recombination as in Xlf-Paxx and Xlf-Atm double Knock Out (DKO) settings. Furthermore, massive apoptosis of post-mitotic neurons causes embryonic lethality of Xrcc4M61R -Nhej1-/- double mutants. These in vivo results reveal new functional interplays between XRCC4 and PAXX, ATM and Xlf in mouse development and provide new insights into the understanding of the clinical manifestations of human XRCC4-deficient condition, in particular its absence of immune deficiency.

    1. Cell Biology
    2. Developmental Biology
    Deepika Sharma et al.
    Research Article

    Osteoblast differentiation is sequentially characterized by high rates of proliferation followed by increased protein and matrix synthesis, processes that require substantial amino acid acquisition and production. How osteoblasts obtain or maintain intracellular amino acid production is poorly understood. Here we identify SLC1A5 as a critical amino acid transporter during bone development. Using a genetic and metabolomic approach, we show SLC1A5 acts cell autonomously to regulate protein synthesis and osteoblast differentiation. SLC1A5 provides both glutamine and asparagine which are essential for osteoblast differentiation. Mechanistically, glutamine and to a lesser extent asparagine support amino acid biosynthesis. Thus, osteoblasts depend on Slc1a5 to provide glutamine and asparagine, which are subsequently used to produce non-essential amino acids and support osteoblast differentiation and bone development.