Endoderm-specific deletion of Tbx1 reveals an FGF-independent role for Tbx1 in pharyngeal apparatus morphogenesis.
Endoderm-specific deletion of Tbx1 reveals an FGF-independent role for Tbx1 in pharyngeal apparatus morphogenesis.
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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
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Basson MA
中科院分区：
文献类型：
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作者：
Jackson A;Kasah S;Mansour SL;Morrow B;Basson MA
T-box转录因子Tbx1对胚胎多器官系统的正常发育至关重要。Tbx1−/−胚胎中最显著的表型之一是尾部咽囊不能从前肠内胚层外翻。尽管对Tbx1在发育中的作用有相当大的兴趣，但Tbx1控制尾侧囊形成的机制仍然难以捉摸。特别是，Tbx1在咽内胚层的表达如何调节小鼠胚胎咽袋的形态发生的问题尚不清楚。为了解决这个问题，我们制作了从咽内胚层特异性删除Tbx1的小鼠胚胎，正如预期的那样，胚胎未能形成尾部咽囊。为了确定分子机制，我们检测了Fgf3和Fgf8配体和下游效应物的表达。虽然Fgf8的表达在tbx1缺陷的内胚层中大大降低，但FGF信号水平不受影响。此外，内胚层中Fgf3和Fgf8的缺失只会部分干扰育儿袋的形成，这表明两者都不是育儿袋形成所必需的。来自咽内皮的Tbx1缺失足以引起尾端咽弓分割缺陷，该缺陷由不依赖于fgf的效应物引起，有待鉴定。
The T-box transcription factor Tbx1, is essential for the normal development of multiple organ systems in the embryo. One of the most striking phenotypes in Tbx1−/− embryos is the failure of the caudal pharyngeal pouches to evaginate from the foregut endoderm. Despite considerable interest in the role of Tbx1 in development, the mechanisms whereby Tbx1 controls caudal pouch formation have remained elusive. In particular, the question as to how Tbx1 expression in the pharyngeal endoderm regulates pharyngeal pouch morphogenesis in the mouse embryo is not known. To address this question, we produced mouse embryos in which Tbx1 was specifically deleted from the pharyngeal endoderm and as expected, embryos failed to form caudal pharyngeal pouches. To determine the molecular mechanism, we examined expression of Fgf3 and Fgf8 ligands and downstream effectors. Although Fgf8 expression is greatly reduced in Tbx1-deficient endoderm, FGF signaling levels are unaffected. Furthermore, pouch morphogenesis is only partially perturbed by the loss of both Fgf3 and Fgf8 from the endoderm, indicating that neither are required for pouch formation. Tbx1 deletion from the pharyngeal endoderm is sufficient to cause caudal pharyngeal arch segmentation defects by FGF-independent effectors that remain to be identified.