T-box

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.{{cite journal | last1=Naiche | first1=L.A. | last2=Harrelson | first2=Zachary | last3=Kelly | first3=Robert G. | last4=Papaioannou | first4=Virginia E. | author-link4=Virginia Papaioannou|title=T-Box Genes in Vertebrate Development | journal=Annual Review of Genetics | publisher=Annual Reviews | volume=39 | issue=1 | date=2005-12-01 | issn=0066-4197 | doi=10.1146/annurev.genet.39.073003.105925 | pages=219–239| pmid=16285859 }}

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.{{cite web | title = Entrez Gene: T| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6862}}{{cite journal | vauthors = Edwards YH, Putt W, Lekoape KM, Stott D, Fox M, Hopkinson DA, Sowden J | title = The human homolog T of the mouse T(Brachyury) gene; gene structure, cDNA sequence, and assignment to chromosome 6q27 | journal = Genome Research | volume = 6 | issue = 3 | pages = 226–33 | date = March 1996 | pmid = 8963900 | doi = 10.1101/gr.6.3.226 | doi-access = free }} Brachyury has been found in all bilaterian animals that have been screened, and is also present in the cnidaria.{{cite journal | vauthors = Scholz CB, Technau U | title = The ancestral role of Brachyury: expression of NemBra1 in the basal cnidarian Nematostella vectensis (Anthozoa) | journal = Development Genes and Evolution | volume = 212 | issue = 12 | pages = 563–70 | date = January 2003 | pmid = 12536320 | doi = 10.1007/s00427-002-0272-x | s2cid = 25311702 }}

The mouse Tbxt gene was cloned{{cite journal | vauthors = Herrmann BG, Labeit S, Poustka A, King TR, Lehrach H | title = Cloning of the T gene required in mesoderm formation in the mouse | journal = Nature | volume = 343 | issue = 6259 | pages = 617–22 | date = February 1990 | pmid = 2154694 | doi = 10.1038/343617a0 | bibcode = 1990Natur.343..617H | s2cid = 4365020 }} 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.

The encoded proteins of TBX5 and TBX4 play a role in limb development, and play a major role in limb bud initiation specifically.{{cite journal | vauthors = Tickle C | title = How the embryo makes a limb: determination, polarity and identity | journal = Journal of Anatomy | volume = 227 | issue = 4 | pages = 418–30 | date = October 2015 | pmid = 26249743 | pmc = 4580101 | doi = 10.1111/joa.12361 }} For instance, in chickens TBX4 specifies hindlimb status while Tbx5 specifies forelimb status.{{cite journal | vauthors = Rodriguez-Esteban C, Tsukui T, Yonei S, Magallon J, Tamura K, Izpisua Belmonte JC | title = The T-box genes Tbx4 and Tbx5 regulate limb outgrowth and identity | journal = Nature | volume = 398 | issue = 6730 | pages = 814–8 | date = April 1999 | pmid = 10235264 | doi = 10.1038/19769 | bibcode = 1999Natur.398..814R | s2cid = 4330287 }} The activation of these proteins by Hox genes initiates signaling cascades that involve the Wnt signaling pathway 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.{{cite journal | vauthors = Hasson P, DeLaurier A, Bennett M, Grigorieva E, Naiche LA, Papaioannou VE, Mohun TJ, Logan MP | title = Tbx4 and tbx5 acting in connective tissue are required for limb muscle and tendon patterning | journal = Developmental Cell | volume = 18 | issue = 1 | pages = 148–56 | date = January 2010 | pmid = 20152185 | pmc = 3034643 | doi = 10.1016/j.devcel.2009.11.013 }}

In humans, and some other animals, defects in the TBX5 gene 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.{{Cite web|url=https://ghr.nlm.nih.gov/condition/holt-oram-syndrome|title=Holt–Oram syndrome|date=June 2014|website=Genetics Home Reference|publisher=U.S. National Library of Medicine|access-date=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/ 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.{{cite journal|last=Bossert|first=T|author2=Walther, T|author3=Gummert, J|author4=Hubald, R|author5=Kostelka, M|author6=Mohr, FW|date=October 2002|title=Cardiac malformations associated with the Holt–Oram syndrome—report on a family and review of the literature.|journal=The Thoracic and Cardiovascular Surgeon|volume=50|issue=5|pages=312–4|doi=10.1055/s-2002-34573|pmid=12375192|s2cid=19665997}}

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.{{cite journal | vauthors = Imsland F, McGowan K, Rubin CJ, Henegar C, Sundström E, Berglund J, Schwochow D, Gustafson U, Imsland P, Lindblad-Toh K, Lindgren G, Mikko S, Millon L, Wade C, Schubert M, Orlando L, Penedo MC, Barsh GS, Andersson L | display-authors = 6 | title = Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses | journal = Nature Genetics | volume = 48 | issue = 2 | pages = 152–8 | date = February 2016 | pmid = 26691985 | pmc = 4731265 | doi = 10.1038/ng.3475}}

• {{cite press release |date=December 21, 2015 |title=A horse of a different color: Genetics of camouflage and the dun pattern |website=ScienceDaily |url=https://www.sciencedaily.com/releases/2015/12/151221133612.htm}}

Genes encoding T-box proteins include:

{{div col}}

• TBXT ({{Gene|TBXT}}) the first found (in mice)
• TBR1 ({{Gene|TBR1}})
• TBX1 ({{Gene|TBX1}})
• TBX2 ({{Gene|TBX2}})
• TBX3 ({{Gene|TBX3}})
• TBX4 ({{Gene|TBX4}})
• TBX5 ({{Gene|TBX5}})
• TBX6 ({{Gene|TBX6}})
• TBX10 ({{Gene|TBX10}})
• TBX15 ({{Gene|TBX15}})
• TBX18 ({{Gene|TBX18}})
• TBX19 ({{Gene|TBX19}})
• TBX20 ({{Gene|TBX20}})
• TBX21 ({{Gene|TBX21}})
• TBX22 ({{Gene|TBX22}})

{{div col end}}

• Brachyury
• Homeobox
• Development genes in plants: G-box, I-box, W-box, Z-box

{{Reflist}}

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• {{cite journal | vauthors = Meisler MH | title = Mutation watch: mouse brachyury (T), the T-box gene family, and human disease | journal = Mammalian Genome | volume = 8 | issue = 11 | pages = 799–800 | date = 1997 | pmid = 9337389 | doi = 10.1007/s003359900581 | url = http://deepblue.lib.umich.edu/bitstream/handle/2027.42/42140/335-8-11-799_8n11p799.pdf;jsessionid=6BA755F775C7632A8CF1E67036AF792F?sequence=1 | hdl = 2027.42/42140 | s2cid = 12617264 | hdl-access = free }}

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• {{MeshName|T-Box+Domain+Proteins}}

{{Transcription factors|g4}}

Category:Transcription factors

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