Regulation of Canonical Wnt Signaling by Brachyury is Essential for Posterior Mesoderm Formation

The T box transcription factor Brachyury is essential for the formation of the posterior body in all vertebrates, although its critical transcriptional targets have remained elusive. Loss-of-function studies of mouse Brachyury and the zebrafish Brachyury ortholog Ntl indicated that Brachyury plays a more significant role in higher vertebrates than lower vertebrates. We have identified a second zebrafish Brachyury ortholog (Bra), and show that a combined loss of Ntl and Bra recapitulates the mouse phenotype, demonstrating an ancient role for Brachyury in patterning all but the most anterior somites. Using cell transplantation, we show that the only essential role for Brachyury during somite formation is non-cell autonomous, and demonstrate that Ntl and Bra are required for and can induce expression of the canonical Wnts wnt8 and wnt3a. We propose that a positive autoregulatory loop between Ntl/Bra and canonical Wnt signaling maintains the mesodermal progenitors to facilitate posterior somite development in chordates.