T-box transcription factor T, also known as Brachyury protein, is encoded for in humans and other apes by the TBXT gene. Brachyury functions as a transcription factor within the T-box family of genes. Brachyury homologs have been found in all animals that have been screened, including representatives from the earliest-diverging non-bilaterians (Cnidaria, Placozoa, Porifera, Ctenophora).
History The brachyury mutation was first described in mice by Nadezhda Alexandrovna Dobrovolskaya-Zavadskaya in 1927 as a mutation that affected tail length and sacral vertebrae in heterozygous animals. In homozygous animals, the brachyury mutation is lethal at around embryonic day 10 due to defects in mesoderm formation, notochord differentiation and the absence of structures posterior to the forelimb bud (Dobrovolskaïa-Zavadskaïa, 1927). The name brachyury comes from the Greek brakhus meaning short and oura meaning tail. In 2018, HGNC updated the human gene name from T to TBXT, presumably to overcome difficulties associated with searching for a single letter gene symbol. Tbxt was cloned by Bernhard Herrmann and colleagues and proved to encode a 436 amino acid embryonic nuclear transcription factor. Tbxt binds to a specific DNA element, a near palindromic sequence TCACACCT through a region in its N-terminus, called the T-box. Tbxt is the founding member of the T-box family which in mammals currently consists of 18 T-box genes. The crystal structure of the human brachyury protein was solved in 2017 by Opher Gileadi and colleagues at the Structural Genomics Consortium in Oxford.
Role in development The gene brachyury appears to have a conserved role in defining the midline of a bilaterian organism, and thus the establishment of the anterior-posterior axis; this function is apparent in chordates and molluscs. Its ancestral role, or at least the role it plays in the Cnidaria, appears to be in defining the blastopore. It also defines the mesoderm during gastrulation. Tissue-culture based techniques have demonstrated one of its roles may be in controlling the velocity of cells as they leave the primitive streak. It effects transcription of genes required for mesoderm formation and cellular differentiation. Brachyury has also been shown to help establish the cervical vertebral blueprint during fetal development. The number of cervical vertebrae is highly conserved among all mammals; however, a spontaneous vertebral and spinal dysplasia (VSD) mutation in this gene has been associated with the development of six or fewer cervical vertebrae instead of the usual seven.
Expression In mice, T is expressed 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 hominid evolution
Tail development TBXT is a transcription factor observed in vertebrate organisms. As such, it is primarily responsible for the genotype that codes for tail formation due to its observed role in axial development and the construction of posterior mesoderm within the lumbar and sacral regions. TBXT transcribes genes that form notochord cells, which are responsible for the flexibility, length, and balance of the spine, including tail vertebrae. Because of the role that the transcription factor plays in spinal development, it is cited as being the protein that is primarily responsible for tail development in mammals. However, due to being a genetically-induced phenotype, it is possible for tail-encoding material to be effectively silenced by mutation. This is the mechanism by which the ntl ortholog developed in the hominidae taxa.
… excerpt ends here. Continue reading the full article.
