Intrinsic and extrinsic cues time somite progenitor contribution to the vertebrate primary body axis

  1. Lara Busby
  2. Guillermo Serrano Nájera
  3. Benjamin John Steventon  Is a corresponding author
  1. University of Cambridge, United Kingdom

Abstract

During embryonic development, the timing of events at the cellular level must be coordinated across multiple length scales to ensure the formation of a well-proportioned body plan. This is clear during somitogenesis, where the progenitors must be allocated to the axis over time whilst maintaining a progenitor population for continued elaboration of the body plan. However, the relative importance of intrinsic and extrinsic signals in timing progenitor addition at the single cell level is not yet understood. Heterochronic grafts from older to younger embryos have suggested a level of intrinsic timing whereby later staged cells contribute to more posterior portions of the axis. To determine the precise step at which cells are delayed, we performed single-cell transcriptomic analysis on heterochronic grafts of somite progenitors in the chicken embryo. This revealed a previously undescribed cell state within which heterochronic grafted cells are stalled. The delayed exit of older cells from this state correlates with expression of posterior Hox genes. Using grafting and explant culture, we find that both Hox gene expression and the migratory capabilities of progenitor populations are intrinsically regulated at the population level. However, by grafting varied sizes of tissue, we find that small heterochronic grafts disperse more readily and contribute to more anterior portions of the body axis while still maintaining Hox gene expression. This enhanced dispersion is not replicated in explant culture, suggesting that it is a consequence of interaction between host and donor tissue and thus extrinsic to the donor tissue. Therefore, we demonstrate that the timing of cell dispersion and resulting axis contribution is impacted by a combination of both intrinsic and extrinsic cues.

Data availability

The single cell RNA-sequencing dataset generated in this work is available via the NCBI Gene ExpressionOmnibus (GEO) under the accession code GSE224169.

The following data sets were generated

Article and author information

Author details

  1. Lara Busby

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Guillermo Serrano Nájera

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5841-8408
  3. Benjamin John Steventon

    Department of Genetics, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    bjs57@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7838-839X

Funding

Wellcome Trust (109408/Z/15/Z)

  • Benjamin John Steventon

Leverhulme Trust (RG93881)

  • Guillermo Serrano Nájera

Biotechnology and Biological Sciences Research Council (Studentship)

  • Lara Busby

Wellcome Trust (225360/Z/22/Z)

  • Benjamin John Steventon

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

Reviewing Editor

  1. Didier YR Stainier, Max Planck Institute for Heart and Lung Research, Germany

Version history

  1. Preprint posted: May 10, 2023 (view preprint)
  2. Received: June 26, 2023
  3. Accepted: January 8, 2024
  4. Accepted Manuscript published: January 9, 2024 (version 1)
  5. Version of Record published: February 1, 2024 (version 2)

Copyright

© 2024, Busby 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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  1. Lara Busby
  2. Guillermo Serrano Nájera
  3. Benjamin John Steventon
(2024)
Intrinsic and extrinsic cues time somite progenitor contribution to the vertebrate primary body axis
eLife 13:e90499.
https://doi.org/10.7554/eLife.90499

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https://doi.org/10.7554/eLife.90499

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