biostudies-literatureUnknownKemmler CLSwiss National Science FoundationNIDCR NIH HHSNIDDK NIH HHSNHLBI NIH HHSNHGRI NIH HHSNIGMS NIH HHSThe 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 <i>Brachyury/T/TBXT</i> gene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover three <i>Brachyury</i>-controlling notochord enhancers <i>T3</i>, <i>C</i>, and <i>I</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 <i>Brachyury</i>-driving notochord enhancers with the <i>brachyury/tbxtb</i> loci from diverse lineages of fishes dates their origin to the last common ancestor of jawed vertebrates. Our data define the enhancers for <i>Brachyury/T/TBXTB</i> notochord expression as ancient mechanism in axis development.bioRxiv : the preprint server for biology2023.04.20.536761https://www.ebi.ac.uk/biostudies/studies/S-EPMC10153258biostudies-literatureConserved enhancer logic controls the notochord expression of vertebrate <i>Brachyury</i>.PMC10153258R01 DE024745DP2 HG010013180345F31 HL167580186993R01 HL162304R01 DK129350R01 HG003988R01 DE028599T32 GM141742Visel ASelleri LBraasch IYun MSmolikova JCzarkwiani AMosimann CMoran HROsterwalder MKemmler CLBotschi SKnapp DFitch OELim FFarley EHermosilla Aguayo VMannion BJBurger ARapp VKozmik ZfalseConserved enhancer logic controls the notochord expression of vertebrate <i>Brachyury</i>.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 <i>Brachyury/T/TBXT</i> gene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover three <i>Brachyury</i>-controlling notochord enhancers <i>T3</i>, <i>C</i>, and <i>I</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 <i>Brachyury</i>-driving notochord enhancers with the <i>brachyury/tbxtb</i> loci from diverse lineages of fishes dates their origin to the last common ancestor of jawed vertebrates. Our data define the enhancers for <i>Brachyury/T/TBXTB</i> notochord expression as ancient mechanism in axis development.2023-01-01T00:00:00Z2023 Apr2025-04-19T04:38:59.672Z2025-04-19T04:38:59.672ZS-EPMC101532583713168110.1101/2023.04.20.536761