PUBLICATION
Conserved enhancers control notochord expression of vertebrate Brachyury
- Authors
- Kemmler, C.L., Smolikova, J., Moran, H.R., Mannion, B.J., Knapp, D., Lim, F., Czarkwiani, A., Hermosilla Aguayo, V., Rapp, V., Fitch, O.E., Bötschi, S., Selleri, L., Farley, E., Braasch, I., Yun, M., Visel, A., Osterwalder, M., Mosimann, C., Kozmik, Z., Burger, A.
- ID
- ZDB-PUB-231019-58
- Date
- 2023
- Source
- Nature communications 14: 65946594 (Journal)
- Registered Authors
- Braasch, Ingo, Burger, Alexa, Kemmler, Cassie L., Moran, Hannah, Mosimann, Christian
- Keywords
- none
- MeSH Terms
-
- Animals
- Fetal Proteins/genetics
- Fetal Proteins/metabolism
- Gene Expression Regulation, Developmental
- Humans
- Mammals/genetics
- Mice
- Notochord*/metabolism
- T-Box Domain Proteins/genetics
- T-Box Domain Proteins/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 37852970 Full text @ Nat. Commun.
Citation
Kemmler, C.L., Smolikova, J., Moran, H.R., Mannion, B.J., Knapp, D., Lim, F., Czarkwiani, A., Hermosilla Aguayo, V., Rapp, V., Fitch, O.E., Bötschi, S., Selleri, L., Farley, E., Braasch, I., Yun, M., Visel, A., Osterwalder, M., Mosimann, C., Kozmik, Z., Burger, A. (2023) Conserved enhancers control notochord expression of vertebrate Brachyury. Nature communications. 14:65946594.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping