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Regulatory changes associated with the head to trunk developmental transition.

Patrícia Duarte1, Rion Brattig Correia1, Ana Nóvoa1

  • 1Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156, Oeiras, Portugal.

BMC Biology
|August 8, 2023
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Summary

This study reveals key regulatory network shifts during vertebrate trunk development. Changes in gene regulation and chromatin accessibility control axial extension and progenitor differentiation, ensuring robust embryonic development.

Keywords:
ATAC-seqHead to trunk transitionNr2f2RNA-seqRetinoic acidWnt5a

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Area of Science:

  • Developmental Biology
  • Genomics
  • Molecular Biology

Background:

  • Vertebrate embryonic development involves anterior tissue formation followed by posterior axis extension for trunk and tail development.
  • Major regulatory gene network changes are implicated in the transition from head to trunk formation.
  • The primitive streak and tail bud are key structures driving sequential axis extension.

Purpose of the Study:

  • To investigate the regulatory changes governing the transition into trunk formation during vertebrate embryonic development.
  • To identify alterations in gene regulatory networks and chromatin accessibility during axial extension.
  • To understand the functional impact of Wnt signaling and chromatin modifications on progenitor cell fate.

Main Methods:

  • Generation of differential interaction networks and chromatin accessibility profiles from mouse embryos at embryonic days 7.5 and 8.5.
  • Analysis of changes in cell processes, signaling pathways, and metabolic functions.
  • Functional exploration of Wnt signaling, including Wnt palmitoleoylation, and assessment of chromatin accessibility at regulatory elements.

Main Results:

  • Observed significant changes in cellular processes, including Wnt signaling, ubiquitination, ion dynamics, and lipid metabolism, during the switch to trunk formation.
  • Identified a functional switch in Wnt palmitoleoylation relevance from gastrulation to axial extension and progenitor differentiation.
  • Detected substantial changes in chromatin accessibility, particularly in intergenic regions, with differential transcription factor footprinting, largely independent of retinoic acid.

Conclusions:

  • Provides a comprehensive view of regulatory shifts controlling the transition to axial extension in vertebrate embryonic development.
  • Reveals mechanisms by which cellular context modulates regulatory factor activity for specific biological outcomes.
  • Suggests the existence of redundant enhancers ensuring robust gene expression patterns during development.