Kemmler, Cassie L; Smolikova, Jana; Moran, Hannah R; Mannion, Brandon J; Knapp, Dunja; Lim, Fabian; Czarkwiani, Anna; Hermosilla Aguayo, Viviana; Rapp, Vincent; Fitch, Olivia E; Bötschi, Seraina; Selleri, Licia; Farley, Emma; Braasch, Ingo; Yun, Maximina; Visel, Axel; Osterwalder, Marco; Mosimann, Christian; Kozmik, Zbynek and Burger, Alexa (2023). Conserved enhancers control notochord expression of vertebrate Brachyury. Nature communications, 14(1), p. 6594. Nature Publishing Group 10.1038/s41467-023-42151-3
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The cell type-specific expression of key transcription factors is central to development and disease. Brachyury/T/TBXT is a major transcription factor for gastrulation, tailbud patterning, and notochord formation; however, how its expression is controlled in the mammalian notochord has remained elusive. Here, we identify the complement of notochord-specific enhancers in the mammalian Brachyury/T/TBXT gene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover three conserved Brachyury-controlling notochord enhancers, T3, C, and I, in human, mouse, and marsupial genomes. Acting as Brachyury-responsive, auto-regulatory shadow enhancers, in cis deletion of all three enhancers in mouse abolishes Brachyury/T/Tbxt expression selectively in the notochord, causing specific trunk and neural tube defects without gastrulation or tailbud defects. The three Brachyury-driving notochord enhancers are conserved beyond mammals in the brachyury/tbxtb loci of fishes, dating their origin to the last common ancestor of jawed vertebrates. Our data define the vertebrate enhancers for Brachyury/T/TBXTB notochord expression through an auto-regulatory mechanism that conveys robustness and adaptability as ancient basis for axis development.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe |
UniBE Contributor: |
Rapp, Vincent Lucien Paul, Osterwalder, Marco |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
19 Oct 2023 12:18 |
Last Modified: |
29 Oct 2023 02:26 |
Publisher DOI: |
10.1038/s41467-023-42151-3 |
PubMed ID: |
37852970 |
BORIS DOI: |
10.48350/187295 |
URI: |
https://boris.unibe.ch/id/eprint/187295 |
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