| Popis: |
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 mammalianBrachyury/T/TBXTgene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover threeBrachyury-controlling notochord enhancersT3, C, andIin 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 ofBrachyury-driving notochord enhancers with thebrachyury/tbxtbloci from diverse lineages of fishes dates their origin to the last common ancestor of jawed vertebrates. Our data define the enhancers forBrachyury/T/TBXTBnotochord expression as ancient mechanism in axis development. |
