in the inner cell mass of the blastocyst stage embryo (but not in the majority of mouse embryonic stem cells) followed by the primitive streak (see image). In later development expression is localised to the node and notochord. In Xenopus laevis Xbra (the Xenopus T homologue, also recently renamed t) is expressed in the mesodermal marginal zone of the pre-gastrula embryo followed by localisation to the blastopore and notochord at the mid-gastrula stage. Orthologs The Danio rerio ortholog is known as ntl (no tail) Role in disease Cancer Brachyury is implicated in the initiation and/or progression of a number of tumor types including chordoma, germ cell tumors, hemangioblastoma, GIST, lung cancer, small cell carcinoma of the lung, breast cancer, colon cancer, hepatocellular carcinoma, prostate cancer, and oral squamous carcinoma. In breast cancer brachyury expression is associated with recurrence, metastasis and reduced survival. It is also associated with resistance to tamoxifen and to cytotoxic chemotherapy. In lung cancer brachyury expression is associated with recurrence and decreased survival. It is also associated with resistance to cytotoxic chemotherapy, radiation, and EGFR kinase inhibitors. In prostate cancer brachyury expression is associated with Gleason score, perineural, invasion and capsular invasion. In addition to its role in common cancers, brachyury has been identified as a definitive diagnostic marker, key driver and therapeutic target for chordoma, a rare malignant tumor that arises from remnant notochordal cells lodged in the vertebrae. The evidence regarding brachyury's role in chordoma includes: Brachyury is highly expressed in all chordomas except for the dedifferentiated subtype, which accounts for less than 5% of cases Germ line duplication of the brachyury gene is responsible for familial chordoma. A germline SNP in brachyury is present in 97% of chordoma patients. Somatic amplifications of brachyury are seen in a subset of sporadic chordomas either by aneuploidy or focal duplication. Brachyury is the most selectively essential gene in chordoma relative to other cancer types. Brachyury is associated with a large superenhancer in chordoma tumors and cell lines, and is the most highly expressed superenhancer-associated transcription factor. Brachyury is an important factor in promoting the epithelial–mesenchymal transition (EMT). Cells that over-express brachyury have down-regulated expression of the adhesion molecule E-cadherin, which allows them to undergo EMT. This process is at least partially mediated by the transcription factors AKT and Snail. Overexpression of brachyury has been linked to hepatocellular carcinoma (HCC, also called malignant hepatoma), a common type of