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      Negative feedback on Retinoic Acid by Brachyury guides gastruloid symmetry-breaking

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      bioRxiv

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          Abstract

          Establishment of the vertebrate body plan requires a combination of extra-embryonic signalling to establish morphogen gradients, and an underlying self-assembly mechanism that contributes to pattern regulation and robustness. Gastruloids are aggregates of mouse embryonic stem cells that break morphological symmetry and polarise Brachyury( Bra) expression in the absence of extra-embryonic signals. However, the mechanism by which symmetry breaking occurs is not yet known. During gastrulation and body axis elongation, retinoic acid (RA) and Cyp26a1are polarised along the anteroposterior axis, and this is critical for balancing the decision of cells to self-renew or differentiate. We found that symmetry-breaking in gastruloids is coincident with the separation of Aldh1a2and Cyp26a1expression, and that feedback from Brais critical for maintaining polarised Cyp26a1gene expression in the gastruloid posterior region. Furthermore, we reveal a short temporal window where RA signalling can negatively influence both Braand Cyp26a1expression. These observations lead us to suggest a mechanism of how initial gastruloid patterning, subsequent elongation, and evolving network topologies can create defined boundaries of RA signalling that permits proper axial patterning and gastruloid growth.

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          (View ORCID Profile)
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          Journal
          bioRxiv
          June 04 2023
          Article
          10.1101/2023.06.02.543388
          325f3533-a2ce-4ef7-811e-9846c91fe12b
          © 2023
          History

          Developmental biology,Ecology
          Developmental biology, Ecology

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