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

Published version
Peer-reviewed

Repository DOI


Type

Article

Change log

Authors

Busby, Lara 
Serrano Nájera, Guillermo  ORCID logo  https://orcid.org/0000-0001-5841-8408
Steventon, Benjamin John  ORCID logo  https://orcid.org/0000-0001-7838-839X

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.

Description

Keywords

chicken, developmental biology

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

13

Publisher

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