T-box refers to a group of
transcription factors involved in
embryoniclimb and
heart development.[1] 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.[2]
Members
T-boxes are especially important to the development of embryos, found in
zebrafish oocyte by Bruce et al 2003 and Xenopus laevis oocyte by Xanthos et al 2001. They are also
expressed in later stages, including adult
mouse and
rabbit studied by Szabo et al 2000.[3]
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.[4][5] Brachyury has been found in all
bilaterian animals that have been screened, and is also present in the
cnidaria.[6]
The mouse Tbxt gene was cloned[7] and found to be a 436 amino acid embryonic nuclear
transcription factor. The protein brachyury binds to the T-box through a region at its N-terminus.
Protein activity
The encoded proteins of
TBX5 and
TBX4 play a role in
limb development, and play a major role in
limb bud initiation specifically.[8] For instance, in chickens TBX4 specifies hindlimb status while Tbx5 specifies forelimb status.[9] The activation of these proteins by
Hox genes initiates signaling cascades that involve the
Wnt signaling pathway and
FGF signals in limb buds.[8] 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.[8] Together, TBX5 and TBX4 play a role in patterning the soft tissues (muscles and tendons) of the musculoskeletal system.[10]
Defects
In humans, and some other animals, defects in the
TBX5gene expression 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.[11][12] Seventy-five percent of affected individuals also have
heart defects, most often there is no separation between the left and right
ventricle of the
heart.[13]
TBX3 is associated with
ulnar–mammary syndrome 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.[14]
^Scholz CB, Technau U (January 2003). "The ancestral role of Brachyury: expression of NemBra1 in the basal cnidarian Nematostella vectensis (Anthozoa)". Development Genes and Evolution. 212 (12): 563–70.
doi:
10.1007/s00427-002-0272-x.
PMID12536320.
S2CID25311702.
^"Holt–Oram syndrome". Genetics Home Reference. U.S. National Library of Medicine. June 2014. Retrieved 18 April 2018.
^McDermott DA, Fong JC, Basson CT. Holt–Oram Syndrome. 2004 Jul 20 [Updated 2015 Oct 8]. In Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK1111/
^Bossert, T; Walther, T; Gummert, J; Hubald, R; Kostelka, M; Mohr, FW (October 2002). "Cardiac malformations associated with the Holt–Oram syndrome—report on a family and review of the literature". The Thoracic and Cardiovascular Surgeon. 50 (5): 312–4.
doi:
10.1055/s-2002-34573.
PMID12375192.
S2CID19665997.