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Abstract The cell type-specific expression of key transcription factors is central to development and disease.Brachyury/T/TBXTis 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 mammalianBrachyury/T/TBXTgene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover three conservedBrachyury-controlling notochord enhancers,T3,C, andI, in human, mouse, and marsupial genomes. Acting as Brachyury-responsive, auto-regulatory shadow enhancers,in cisdeletion 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 threeBrachyury-driving notochord enhancers are conserved beyond mammals in thebrachyury/tbxtbloci of fishes, dating their origin to the last common ancestor of jawed vertebrates. Our data define the vertebrate enhancers forBrachyury/T/TBXTBnotochord expression through an auto-regulatory mechanism that conveys robustness and adaptability as ancient basis for axis development.