T-box refers to a group of transcription factors involved in limb and heart development.[1]

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 heart and are responsible for Holt-Oram syndrome.

The encoded proteins of Tbx5 and Tbx4 play a role in limb development, and play a major role in limb bud initiation specifically.[2] For instance, in chickens Tbx4 specifies hindlimb status while Tbx5 specifies forelimb status.[3] The activation of these proteins by Hox genes initiates signaling cascades that involve the Wnt signaling pathway and FGF signals in limb buds.[2] 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.[2] Together, Tbx5 and Tbx4 play a role in patterning the soft tissues (muscles and tendons) of the musculoskeletal system.[4]

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.[5]

Genes encoding T-box proteins include:

See also


  1. ^ Wilson V, Conlon FL (2002). "The T-box family". Genome Biol. 3 (6): REVIEWS3008. doi:10.1186/gb-2002-3-6-reviews3008. PMC 139375Freely accessible. PMID 12093383. 
  2. ^ a b c . PMID 26249743.  Missing or empty title= (help)
  3. ^ . PMID 10235264.  Missing or empty title= (help)
  4. ^ Hasson, Peleg; DeLaurier, April; Bennett, Michael; Grigorieva, Elena; Naice, L.A.; Papaioannou, Virginia E.; Mohun, Timothy J.; Logan, Malcolm P.O. (2010). "Tbx4 and Tbx5 acting in connective tissue are required for limb muscle and tendon patterning". Developmental Cell. 18 (1): 148–156. doi:10.1016/j.devcel.2009.11.013. PMC 3034643Freely accessible. PMID 20152185. 
  5. ^ "A Horse of a Different Color: Genetics of camouflage and the dun pattern". Science Daily. December 21, 2015. Retrieved June 25, 2016. 

Further reading

External links