Pharyngeal epithelial deletion of Tbx1 causes caudal pharyngeal arch defect but not cardiac conotruncal anomaly.
Pharyngeal epithelial deletion of Tbx1 causes caudal pharyngeal arch defect but not cardiac conotruncal anomaly.
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Tbx1 的咽上皮缺失会导致尾部咽弓缺损，但不会导致心脏圆锥干异常。
DOI：
10.1016/j.bbrc.2020.10.011
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Zhang Zhen
中科院分区：
文献类型：
--
作者：
Wei Lu;Wang Wenfeng;Yang Junjie;Huang Xu;Baldini Antonio;Zhang Zhen
TBX 1是22q11.2缺失综合征（22q11.2DS）的主要致病基因。它在咽器的三个胚层中均有表达，控制着复杂的形态发生。主动脉弓构型缺陷是由咽部内胚层或外胚层的单倍性不足引起的，而不是由中胚层引起的。然而，中胚层Tbx 1缺失引起的咽部和心血管缺损比咽部内胚层或外胚层Tbx 1缺失更严重。这与传统的认为咽上皮内陷导致咽部分割的观点不一致。因此，我们想知道咽外胚层和外胚层Tbx 1是否可以相互补偿。在这里，我们仔细地表征了咽上皮特异性Fgf 15 CreandFgf 15 HspCrelines，并使用它们进行咽上皮特异性缺失。我们的数据显示，具有主动脉弓构型缺陷的E18.5Fgf15Cre; Tbx 1flox/+胚胎的百分比与具有第四咽弓动脉（PAA）缺陷的E10.5Fgf15Cre; Tbx 1flox/+胚胎的百分比相似，表明与种系单倍性缺陷相反，没有从初始PAA缺陷显著恢复。Tbx 1flox/Tbx胚胎有发育不良的尾咽弓和有缺陷的衍生物，但心脏OFT发育不受影响。在咽外胚层和内胚层中的异常Tbx 1缺失的表型谱与单个咽内胚层或外胚层特异性Tbx 1缺失的表型谱惊人地相似。协同效应的缺乏表明咽内胚层和外胚层之间密切的地形相互作用，通过该组织中的基因的缺失可能会破坏相邻组织的发育，从而导致在任一组织特异性缺失中相似的形态表型。
TBX1is a major disease gene of 22q11.2 deletion syndrome (22q11.2DS). It is expressed in all three germ layers of pharyngeal apparatus to control the complicated morphogenesis. The haploinsufficiency of pharyngeal endodermal or ectodermal, but not mesodermalTbx1causes aortic arch patterning defect. However, the mesodermal deletion ofTbx1causes much severer pharyngeal and cardiovascular defect than either pharyngeal endodermal or ectodermalTbx1deletion does. It is inconsistent with the conventional thought that the invagination of pharyngeal epithelia drives pharyngeal segmentation. Therefore, we asked whether pharyngeal ectodermal and ectodermalTbx1can compensate the loss of each other. Here we carefully characterized pharyngeal epithelia-specificFgf15CreandFgf15HspCrelines and used them to perform pharyngeal epithelia-specific deletion. Our data showed that the percentage of E18.5Fgf15Cre;Tbx1flox/+embryos with aortic arch patterning defects was similar to that of E10.5Fgf15Cre;Tbx1flox/+embryos with the 4th pharyngeal arch artery (PAA) defect, indicating that there is no significant recovery from the initial PAA defect, in contrast to germ line haploinsufficiency.Fgf15Cre;Tbx1flox/floxembryos had hypoplastic caudal pharyngeal arch and defective derivatives, but cardiac OFT development was not affected. The phenotypic spectrum of simultaneousTbx1deletion in both pharyngeal ectoderm and endoderm is strikingly similar to what presents with single pharyngeal endoderm or ectoderm-specific deletion ofTbx1. The absence of synergistic effect indicates intimate topographic interactions among pharyngeal endoderm and ectoderm, through which deletion of a gene in one tissue may disrupt the development of adjacent tissues and thereby lead to similar morphological phenotypes in either tissue-specific deletion.
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影响因子：
4.6
作者：
Piotrowski, T;Ahn, DG;Ho, RK
通讯作者：
Ho, RK
影响因子：
3.5
作者：
Kelly, RG;Jerome-Majewska, LA;Papaioannou, VE
通讯作者：
Papaioannou, VE
内胚层特异性缺失Tbx1揭示了Tbx1在咽器形态发生中不依赖于FGF的作用。
DOI：
10.1002/dvdy.24147
发表时间：
2014-09
期刊：
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子：
--
作者：
Jackson A;Kasah S;Mansour SL;Morrow B;Basson MA
通讯作者：
Basson MA
影响因子：
64.5
作者：
Merscher, S;Funke, B;Kucherlapati, R
通讯作者：
Kucherlapati, R
影响因子：
3.5
作者：
Shaikh, TH;Kurahashi, H;Emanuel, BS
通讯作者：
Emanuel, BS