T-box refers to a group of

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...

s involved in embryonic

limb Limb may refer to: Science and technology * Limb (anatomy), an appendage of a human or animal *Limb, a large or main branch of a tree *Limb, in astronomy, the curved edge of the apparent disk of a celestial body, e.g. lunar limb *Limb, in botany, ...

and

heart The heart is a muscular Organ (biology), organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as ca ...

development. Every T-box protein has a relatively large DNA-binding domain, generally comprising about a third of the entire protein that is both necessary and sufficient for sequence-specific DNA binding. All members of the T-box gene family bind to the "T-box", a DNA consensus sequence of TCACACCT.

Members

T-boxes are especially important to the development of embryos, found in

zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family (Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ca ...

oocyte by Bruce et al 2003 and ''

Xenopus laevis The African clawed frog (''Xenopus laevis'', also known as the xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the three short claws o ...

'' oocyte by Xanthos et al 2001. They are also expressed in later stages, including adult

mouse A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

and

rabbit Rabbits, also known as bunnies or bunny rabbits, are small mammals in the family Leporidae (which also contains the hares) of the order Lagomorpha (which also contains the pikas). ''Oryctolagus cuniculus'' includes the European rabbit sp ...

studied by Szabo et al 2000. Mutations in the first one found caused short tails in mice, and thus the protein encoded was named brachyury, Greek for "short-tail". In mice this gene is named ''Tbxt'', and in humans it is named ''TBXT''. Brachyury has been found in all

bilateria The Bilateria or bilaterians are animals with bilateral symmetry as an embryo, i.e. having a left and a right side that are mirror images of each other. This also means they have a head and a tail (anterior-posterior axis) as well as a belly and ...

n animals that have been screened, and is also present in the

cnidaria Cnidaria () is a phylum under kingdom Animalia containing over 11,000 species of aquatic animals found both in freshwater and marine environments, predominantly the latter. Their distinguishing feature is cnidocytes, specialized cells that ...

. The mouse ''Tbxt'' gene was cloned, and proved that brachyury was a 436 amino acid embryonic nuclear

. Brachyury binds to the T-box, through a region at its N-terminus.

Protein activity

The encoded proteins of

TBX5 T-box transcription factor TBX5, (T-box protein 5) is a protein that in humans is encoded by the ''TBX5'' gene. This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes ...

and TBX4 play a role in limb development, and play a major role in

limb bud The limb bud is a structure formed early in vertebrate limb development. As a result of interactions between the ectoderm and underlying mesoderm, formation occurs roughly around the fourth week of development. In the development of the human em ...

initiation specifically. For instance, in chickens TBX4 specifies hindlimb status while Tbx5 specifies forelimb status. The activation of these proteins by

Hox gene Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the cor ...

s initiates signaling cascades that involve the

Wnt signaling pathway The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling ...

and FGF signals in limb buds. Ultimately, TBX4 and TBX5 lead to the development of apical ectodermal ridge (AER) and zone of polarizing activity (ZPA) signaling centers in the developing limb bud, which specify the orientation growth of the developing limb. Together, TBX5 and TBX4 play a role in patterning the soft tissues (muscles and tendons) of the musculoskeletal system.

Defects

In humans, and some other animals, defects in the

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. T ...

are responsible for Holt–Oram syndrome, which is characterized by at least one abnormal wrist bone. Other arm bones are almost always affected, though the severity can vary widely, from complete absence of a bone, to only a reduction in bone length.McDermott DA, Fong JC, Basson CT. Holt–Oram Syndrome. 2004 Jul 20 pdated 2015 Oct 8 In Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® nternet Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1111/ Seventy-five percent of affected individuals also have

heart defects A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...

, most often there is no separation between the left and right ventricle of the

TBX3 T-box transcription factor TBX3 is a protein that in humans is encoded by the ''TBX3'' gene. T-box 3 (TBX3) is a member of the T-box gene family of transcription factors which all share a highly conserved DNA binding domain known as the T-box. Th ...

is associated with

ulnar–mammary syndrome Ulnar–mammary syndrome or Schinzel syndrome is a cutaneous condition characterized by nipple and breast hypoplasia or aplasia. Features of UMS can be mild to severe and can vary significantly from person to person, even within the same family. ...

in humans, but is also responsible for the presence or absence of dun color in horses, and has no deleterious effects whether expressed or not. *

T-box genes

Genes encoding T-box proteins include: * TBXT () the first found (in mice) *

TBR1 T-box, brain, 1 is a transcription factor protein important in vertebrate embryo development. It is encoded by the ''TBR1'' gene. This gene is also known by several other names: ''T-Brain 1'', ''TBR-1'', ''TES-56'', and ''MGC141978''. TBR1 is a ...

() * TBX1 () *

TBX2 T-box transcription factor 2 Tbx2 is a transcription factor that is encoded by the ''Tbx2'' gene on chromosome 17q21-22 in humans. This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T ...

() *

() * TBX4 () *

() * TBX6 () * TBX10 () * TBX15 () * TBX18 () *

TBX19 T-box transcription factor TBX19 is a protein that in humans is encoded by the ''TBX19'' gene. This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcript ...

() * TBX20 () * TBX21 () * TBX22 ()

References

External links

* Transcription factors {{protein-stub