22q11 Deletion Syndrome: A Role for TBX1 in Pharyngeal and Cardiovascular Development
22q11 Deletion Syndrome: A Role for TBX1 in Pharyngeal and Cardiovascular Development
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DOI：
10.1007/s00246-009-9613-0
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发表时间：
2010-04-01
影响因子：
1.6
通讯作者：
Scambler, Peter J.
中科院分区：
文献类型：
--
作者：
Scambler, Peter J.
Tbx1是结合域转录因子Tbox家族的成员。TBX1在DiGeorge或velocardiofacial综合征患者22q11区域内缺失Tbx1单倍不足的小鼠具有概括该综合征的主要特征的表型，特别是咽弓动脉的异常生长和重塑。Tbx1单倍不足表型通过遗传背景和推定下游靶点的突变进行修饰。Tbx1的纯合无效突变具有更严重的缺陷，包括流出道分隔失败和尾咽弓缺失。Tbx1是一种转录激活因子，这种活性的丧失与参与心血管形态发生的各种基因表达的改变有关。特别是，成纤维细胞生长因子和视黄酸信号失调的Tbx1突变体。本文总结了Tbx1的组织特异性和时间需求，并试图综合了解其控制下的发育途径。
Tbx1 is a member of the Tbox family of binding domain transcription factors. TBX1 maps within the region of 22q11 deleted in humans with DiGeorge or velocardiofacial syndrome. Mice haploinsufficient for Tbx1 have phenotypes that recapitulate major features of the syndrome, notably abnormal growth and remodelling of the pharyngeal arch arteries. The Tbx1 haploinsufficiency phenotype is modified by genetic background and by mutations in putative downstream targets. Homozygous null mutations of Tbx1 have more severe defects including failure of outflow tract septation, and absence of the caudal pharyngeal arches. Tbx1 is a transcriptional activator, and loss of this activity has been linked to alterations in the expression of various genes involved in cardiovascular morphogenesis. In particular, Fgf and retinoic acid signalling are dysregulated in Tbx1 mutants. This article summarises the tissue specific and temporal requirements for Tbx1, and attempts to synthesis what is know about the developmental pathways under its control.