When Brachyury meets Smad1: the evolution of bilateral symmetry during gastrulation

Understanding the events that led to the emergence of the bilaterians is a daunting task, impaired by the huge evolutionary gap separating us from the pre-Cambrian. During gastrulation, the expression of the transcription factor Brachyury is remarkably well conserved around the blastopore of bilaterians and cnidarians. Only the bilaterian Brachyury proteins, however, share a distinctive N-terminal sequence not found in outgroups such as cnidarians, sponges or placozoans. We now know that, in vertebrates, this N-terminal domain confers specific transcriptional activity, by recruiting Smad1, the first identified co-factor for Brachyury. Smad1 is an effector of the BMP pathway, and has been isolated in bilaterians and cnidarians. Here, I propose that the protein-protein interaction between Brachyury and Smad1 represents an evolutionary novelty of the Urbilateria. The gain of the N-terminal domain might have been selected to spatially modulate the activity of Brachyury, thereby facilitating the establishment of bilateral symmetry during gastrulation movements.