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

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Serrano Nájera, Guillermo  ORCID logo
Steventon, Benjamin John  ORCID logo


jats:pDuring 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 jats:italicHox</jats:italic> genes. Using grafting and explant culture, we find that both jats:italicHox</jats:italic> 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 jats:italicHox</jats:italic> 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.</jats:p>


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Acknowledgements: LB was supported by a BBSRC DTP Studentship, GSN was supported by a research grant from the Leverhulme Trust (RG93881), and BS was supported by a Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (109408/Z/15/Z). We thank Alexandra Neaverson, Val Wilson, Stephane Nédélec, and Kate McDole for valuable feedback.


Hox, chicken, developmental biology, gastrulation, primitive streak, somitogenesis, timing, Animals, Chick Embryo, Somites, Cues, Gene Expression Regulation, Developmental, Vertebrates, Genes, Homeobox

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eLife Sciences Publications Ltd
Wellcome Trust (109408/Z/15/Z)
Leverhulme Trust (ECF-2022-474)
Isaac Newton Trust (22.08(d))
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