Brachyury
Encyclopedia
Brachyury is a protein
that in humans is encoded by the T gene
. Brachyury is a transcription factor
within the T-box complex of genes. It has been found in all bilateria
n animals that have been screened, and is also present in the cnidaria
.
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 and proved to encode an 436 amino acid embroynic 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.
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.
Transcription of genes required for mesoderm formation and cellular differentiation
.
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)
, a malignant tumor that arises from remnant notochordal cells lodged in the vertebrae. 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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the T gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. Brachyury is a transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
within the T-box complex of genes. It has been found in all bilateria
Bilateria
The bilateria are all animals having a bilateral symmetry, i.e. they have a front and a back end, as well as an upside and downside. Radially symmetrical animals like jellyfish have a topside and downside, but no front and back...
n animals that have been screened, and is also present in the cnidaria
Cnidaria
Cnidaria is a phylum containing over 9,000 species of animals found exclusively in aquatic and mostly marine environments. Their distinguishing feature is cnidocytes, specialized cells that they use mainly for capturing prey. Their bodies consist of mesoglea, a non-living jelly-like substance,...
.
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 and is lethal in homozygous animals around embryonic day 10 due to defects in mesodermMesoderm
In all bilaterian animals, the mesoderm is one of the three primary germ cell layers in the very early embryo. The other two layers are the ectoderm and endoderm , with the mesoderm as the middle layer between them.The mesoderm forms mesenchyme , mesothelium, non-epithelial blood corpuscles and...
formation, notochord
Notochord
The notochord is a flexible, rod-shaped body found in embryos of all chordates. It is composed of cells derived from the mesoderm and defines the primitive axis of the embryo. In some chordates, it persists throughout life as the main axial support of the body, while in most vertebrates it becomes...
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 and proved to encode an 436 amino acid embroynic nuclear transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
. 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
T-box
T-box refers to a group of transcription factors involved in limb and heart development. In humans and some other animals, defects in the TBX5 gene expression can lead to finger-like thumbs and ventricular septal defects in which there is no separation between the left and right ventricle of the...
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, 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
Blastopore
A blastopore is an opening into the archenteron during the embryonic stages of an organism. The distinction between protostomes and deuterostomes is based on the direction in which the mouth develops in relation to the blastopore...
. It also defines the mesoderm during gastrulation.
Transcription of genes required for mesoderm formation and cellular differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
.
Expression
In mice T is expressed in the inner cell massInner cell mass
In early embryogenesis of most eutherian mammals, the inner cell mass is the mass of cells inside the primordial embryo that will eventually give rise to the definitive structures of the fetus...
of the blastocyst
Blastocyst
The blastocyst is a structure formed in the early embryogenesis of mammals, after the formation of the morula. It is a specifically mammalian example of a blastula. It possesses an inner cell mass , or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast,...
stage embryo (but not in the majority of mouse embryonic stem cells) followed by the primitive streak
Primitive streak
The primitive streak is a structure that forms during the early stages of avian, reptilian and mammalian embryonic development.-Introduction:...
(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
Danio rerio
The zebrafish, Danio rerio, is a tropical freshwater fish belonging to the minnow family of order Cypriniformes. It is a popular aquarium fish, frequently sold under the trade name zebra danio, and is an important vertebrate model organism in scientific research.-Taxonomy:The zebrafish are...
homologue is known as ntl (no tail)
Cancer
Expression of the brachyury gene has been identified as a definitive diagnostic marker of chordomaChordoma
Chordoma is a rare slow-growing malignant neoplasm thought to arise from cellular remnants of the notochord. The evidence for this is the location of the tumors , the similar immunohistochemical staining patterns, and the demonstration that notochordal cells are preferentially left behind in the...
, a malignant tumor that arises from remnant notochordal cells lodged in the vertebrae. 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
Epithelial-mesenchymal transition
Epithelial-mesenchymal transition or transformation is a hypothesized program of development of biological cells characterized by loss of cell adhesion, repression of E-cadherin expression, and increased cell mobility...
and promotes invasion.
See also
- Homeobox protein NANOG
- POU5F1
- SOX2SOX2SRY -box 2, also known as SOX2, is a transcription factor that is essential to maintain self-renewal of undifferentiated embryonic stem cells....
- MIXL1
- GSCGSCGSC could refer to:* Game score, a baseball statistic abbreviated as "GSc"* Game Stock Car, a racing simulator developed by Reiza Studios.* Air Force Global Strike Command, a major command of the United States Air Force* GSC bus* Global Security Challenge...
- EOMES
- Transcription factors
- Gene regulatory networkGene regulatory networkA gene regulatory network or genetic regulatory network is a collection of DNA segments in a cell whichinteract with each other indirectly and with other substances in the cell, thereby governing the rates at which genes in the network are transcribed into mRNA.In general, each mRNA molecule goes...
- BioinformaticsBioinformaticsBioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
- ChordomaChordomaChordoma is a rare slow-growing malignant neoplasm thought to arise from cellular remnants of the notochord. The evidence for this is the location of the tumors , the similar immunohistochemical staining patterns, and the demonstration that notochordal cells are preferentially left behind in the...
External links
- Mouse Genome Informatics entry for T
- European Bioinformatics Institute InterPro entry for Brachyury
- Information Hyperlinked Over Proteins entry for Brachyury
- XenbaseXenbaseXenbase is a model organism database, providing informatics resources, genomic and biological data on the frogs, Xenopus laevis and Xenopus tropicalis.-Xenopus as a model organism:...
Gene entry for t