Ryan Kenneth, Chin Alvin J
Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Joseph Stokes Jr. Research Institute, Division of Cardiology, Abramson Research Center, Philadelphia, Pennsylvania, USA.
Birth Defects Res C Embryo Today. 2003 Feb;69(1):25-37. doi: 10.1002/bdrc.10001.
T-box genes play roles in vertebrate gastrulation and in later organogenesis. Their existence in all metazoans examined so far indicates that this is an evolutionarily ancient gene family. Drosophila melanogaster has eight T-box genes, whereas Caenorhabditis elegans has 22. Mammals appear to have at least 18 T-box genes, comprising five subfamilies.
A full range of cytological, developmental, molecular and genetic methodologies have recently been applied to the study of T-box genes.
Over the last 5 years, mutations in TBX1 and TBX5 have been implicated in two human disorders with haplo-insufficient cardiovascular phenotypes, DiGeorge/velocardiofacial syndrome and Holt-Oram ("heart-hand") syndrome. Interestingly, the number of T-box gene family members discovered to have cardiac or pharyngeal arch expression domains during vertebrate embryonic development has steadily grown. In addition, various Tbx5 loss-of-function models in organisms as distant as the mouse and zebrafish do indeed phenocopy Holt-Oram syndrome. Finally, the intriguing discovery earlier this year that a T-box gene is expressed in a subset of cardioblasts in D. melanogaster suggests that members of this gene family may have fundamental, conserved roles in cardiovascular pattern formation.
These developments prompted us to review the current understanding of the contribution of T-box genes to cardiovascular morphogenesis.
T-box基因在脊椎动物原肠胚形成及后期器官发生过程中发挥作用。在目前已检测的所有后生动物中均存在该基因，这表明它是一个进化上古老的基因家族。黑腹果蝇有8个T-box基因，秀丽隐杆线虫有22个。哺乳动物似乎至少有18个T-box基因，分为5个亚家族。
最近一系列细胞学、发育学、分子学及遗传学方法已应用于T-box基因的研究。
在过去5年中，TBX1和TBX5的突变已与两种单倍体不足的心血管表型人类疾病相关，即迪格奥尔格/腭心面综合征和霍尔特-奥拉姆（“心-手”）综合征。有趣的是，在脊椎动物胚胎发育过程中，发现具有心脏或咽弓表达域的T-box基因家族成员数量稳步增加。此外，在小鼠和斑马鱼等不同生物体中的各种Tbx5功能丧失模型确实模拟了霍尔特-奥拉姆综合征。最后，今年早些时候一个有趣的发现是，一个T-box基因在黑腹果蝇的一部分成 cardioblasts中表达，这表明该基因家族成员可能在心血管模式形成中具有基本的、保守的作用。
这些进展促使我们回顾目前对T-box基因在心血管形态发生中作用的理解。
