학술논문
Conserved enhancer logic controls the notochord expression of vertebrate Brachyury
Document Type
article
Author
Kemmler, Cassie L; Smolikova, Jana; Moran, Hannah R; Mannion, Brandon J; Knapp, Dunja; Lim, Fabian; Czarkwiani, Anna; Aguayo, Viviana Hermosilla; Rapp, Vincent; Fitch, Olivia E; Bötschi, Seraina; Selleri, Licia; Farley, Emma; Braasch, Ingo; Yun, Maximina; Visel, Axel; Osterwalder, Marco; Mosimann, Christian; Kozmik, Zbynek; Burger, Alexa
Source
bioRxiv. 4(05-02)
Subject
Language
Abstract
The cell type-specific expression of key transcription factors is central to development. 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 Brachyury -controlling notochord enhancers T3, C , and I in human, mouse, and marsupial genomes. Acting as Brachyury-responsive, auto-regulatory shadow enhancers, deletion of all three enhancers in mouse abolishes Brachyury/T expression selectively in the notochord, causing specific trunk and neural tube defects without gastrulation or tailbud defects. Sequence and functional conservation of Brachyury -driving notochord enhancers with the brachyury/tbxtb loci from diverse lineages of fishes dates their origin to the last common ancestor of jawed vertebrates. Our data define the enhancers for Brachyury/T/TBXTB notochord expression as ancient mechanism in axis development.