Evolution and Classification of the T-Box Transcription Factor Family.

T-box proteins are key developmental transcription factors in Metazoa. Until recently they were thought to be animal specific and many T-box classes were considered bilaterian specific. Recent genome data from both early-branching animals and their closest unicellular relatives have radically changed this scenario. Thus, we now know that T-box genes originated in premetazoans, being present in the genomes of some extant early-branching fungi and unicellular holozoans. Here, we update the evolutionary classification of T-box families and review the evolution of T-box function in early-branching animals (sponges, ctenophores, placozoans, and cnidarians) and nonmodel bilaterians. We show that concomitant with the origin of Metazoa, the T-box family radiated into the major known T-box classes. On the other hand, while functional studies are still missing for many T-box classes, the emerging picture is that T-box genes have key roles in multiple aspects of development and in adult terminal cell-type differentiation in different animal lineages. A paradigmatic example is that of Brachyury, the founding member of the T-box family, for which several studies indicate a widely conserved role in regulating cell motility in different animal lineages and probably even before the advent of animal multicellularity. Overall, we here review the evolutionary history of T-box genes from holozoans to animals and discuss both their functional diversity and conservation.