Fgf8 expression in the Tbx1 domain causes skeletal abnormalities and modifies the aortic arch but not the outflow tract phenotype of Tbx1 mutants.
Fgf8 expression in the Tbx1 domain causes skeletal abnormalities and modifies the aortic arch but not the outflow tract phenotype of Tbx1 mutants.
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DOI：
10.1016/j.ydbio.2006.03.044
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发表时间：
2006-07
影响因子：
2.7
通讯作者：
F. Vitelli;Zhen Zhang;Tuong Huynh;Angela Sobotka;Annalisa Mupo;A. Baldini
中科院分区：
文献类型：
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作者：
F. Vitelli;Zhen Zhang;Tuong Huynh;Angela Sobotka;Annalisa Mupo;A. Baldini
Fgf 8和Tbx 1已被证明在主动脉弓的形成中相互作用，并且这两种基因在心脏流出道的形成和生长中都是必需的。然而，这两个基因相互作用的性质尚不清楚。我们利用了一个新的Tbx 1Fgf 8等位基因，驱动Fgf 8在Tbx 1阳性细胞中的表达和诱导型Cre-LoxP重组系统，以解决Fgf 8在Tbx 1阳性细胞中调节心血管发育的作用。结果支持Tbx 1表达细胞中Fgf 8的需求，以精细地控制主动脉弓和大动脉的模式，特别是在咽弓动脉重塑过程中，并表明内胚层是这种相互作用的最可能的位点。此外，我们的数据表明，Fgf 8和Tbx 1发挥独立的作用，在调节流出道的发展。这一发现具有临床相关性，因为TBX 1是DGS/VCFS的候选者，其临床特征为心血管缺陷的可变表达性和降低的表达率; Fgf 8基因变体可能为这种变异性提供分子线索。
Fgf8 and Tbx1 have been shown to interact in patterning the aortic arch, and both genes are required in formation and growth of the outflow tract of the heart. However, the nature of the interaction of the two genes is unclear. We have utilized a novel Tbx1Fgf8allele which drives Fgf8 expression in Tbx1-positive cells and an inducible Cre-LoxP recombination system to address the role of Fgf8 in Tbx1 positive cells in modulating cardiovascular development. Results support a requirement of Fgf8 in Tbx1 expressing cells to finely control patterning of the aortic arch and great arteries specifically during the pharyngeal arch artery remodeling process and indicate that the endoderm is the most likely site of this interaction. Furthermore, our data suggest that Fgf8 and Tbx1 play independent roles in regulating outflow tract development. This finding is clinically relevant since TBX1 is the candidate for DGS/VCFS, characterized clinically by variable expressivity and reduced penetrance of cardiovascular defects; Fgf8 gene variants may provide molecular clues to this variability.