Brachyury
Brachyury is a protein that in humans is encoded by the T gene.[1][2] Brachyury is a transcription factor within the T-box complex of genes.[3] It has been found in all bilaterian animals that have been screened, and is also present in the cnidaria.[3]
History
The brachyury mutation was first described in mice by Nadine Dobrovolskaïa-Zavadskaïa 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 forlimb bud (Dobrovolskaïa-Zavadskaïa, 1927). The name brachyury comes from the Greek brakhus meaning short and oura meaning tail.
According to human and mouse genome nomenclature, brachyury now has the symbol and gene name T although brachyury is maintained as the gene description.
The mouse T gene was cloned by Bernhard Herrmann and colleagues[4] and proved to encode an 436 amino acid embryonic nuclear transcription factor. T binds to a specific DNA element, a near palindromic sequence TCACACCT through a region in its N-terminus, called the T-box. T is the founding member of the T-box family which in mammals currently consists of 18 T-box genes.
Function
The gene brachyury appears to have a conserved role in defining the midline of a bilaterian organism,[5] and thus the establishment of the anterior-posterior axis; this function is apparent in chordates and molluscs.[6] Its ancestral role, or at least the role it plays in the Cnidaria, appears to be in defining the blastopore.[3] It also defines the mesoderm during gastrulation.[7]
Transcription of genes required for mesoderm formation and cellular differentiation.
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.
The Danio rerio homologue is known as ntl (no tail)
Cancer
Expression of the brachyury gene has been identified as a definitive diagnostic marker of chordoma, a malignant tumor that arises from remnant notochordal cells lodged in the vertebrae.[8] Furthermore, germ line duplication of brachyury confers major susceptibility to chordoma. The chromosomal region on 6q27 containing the brachyury gene was gained in 6 of 21 chordomas (29%), and none of the 21 chordomas analyzed showed deletions that could have affected this gene.
Brachyury is overexpressed in a number of tumor types. It mediates epithelial-mesenchymal transition and promotes invasion.
See also
- Homeobox protein NANOG
- POU5F1
- SOX2
- MIXL1
- GSC
- EOMES
- Transcription factors
- Gene regulatory network
- Bioinformatics
- Chordoma
References
- ↑ "Entrez Gene: T".
- ↑ Edwards YH, Putt W, Lekoape KM, Stott D, Fox M, Hopkinson DA, Sowden J (March 1996). "The human homolog T of the mouse T(Brachyury) gene; gene structure, cDNA sequence, and assignment to chromosome 6q27". Genome Res. 6 (3): 226–33. doi:10.1101/gr.6.3.226. PMID 8963900.
- ↑ 3.0 3.1 3.2 Scholz CB, Technau U (January 2003). "The ancestral role of Brachyury: expression of NemBra1 in the basal cnidarian Nematostella vectensis (Anthozoa)". Dev. Genes Evol. 212 (12): 563–70. doi:10.1007/s00427-002-0272-x. PMID 12536320.
- ↑ Herrmann BG, Labeit S, Poustka A, King TR, Lehrach H (February 1990). "Cloning of the T gene required in mesoderm formation in the mouse". Nature 343 (6259): 617–22. doi:10.1038/343617a0. PMID 2154694.
- ↑ Le Gouar, M.; Guillou, A.; Vervoort, M. (2004). "Expression of a SoxB and a Wnt2/13 gene during the development of the mollusc Patella vulgata.". Development genes and evolution 214 (5): 250–256. doi:10.1007/s00427-004-0399-z. PMID 15034714.
- ↑ Lartillot, N; Lespinet, O; Vervoort, M; Adoutte, A (2002). "Expression pattern of Brachyury in the mollusc Patella vulgata suggests a conserved role in the establishment of the AP axis in Bilateria.". Development 129 (6): 1411–1421. PMID 11880350.
- ↑ Marcellini, S.; Technau, U.; Smith, J.; Lemaire, P. (2003). "Evolution of Brachyury proteins: identification of a novel regulatory domain conserved within Bilateria". Developmental Biology 260 (2): 352–361. doi:10.1016/S0012-1606(03)00244-6. PMID 12921737.
- ↑ Vujovic S, Henderson S, Presneau N, Odell E, Jacques TS, Tirabosco R, Boshoff C, Flanagan AM (June 2006). "Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas". J. Pathol. 209 (2): 157–65. doi:10.1002/path.1969. PMID 16538613.
Further reading
- Yoshikawa T, Piao Y, Zhong J, Matoba R, Carter MG, Wang Y, Goldberg I, Ko MS (January 2006). "High-throughput screen for genes predominantly expressed in the ICM of mouse blastocysts by whole mount in situ hybridization". Gene Expr. Patterns 6 (2): 213–24. doi:10.1016/j.modgep.2005.06.003. PMC 1850761. PMID 16325481.
- Meisler (1997). Mutation watch: Mouse brachyury (T), the T-box gene family, and human disease..
External links
- Mouse Genome Informatics entry for T
- European Bioinformatics Institute InterPro entry for Brachyury
- Information Hyperlinked Over Proteins entry for Brachyury
- Xenbase Gene entry for t
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