GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo
GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo
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DOI：
10.1242/dev.02720
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发表时间：
2007-01-01
期刊：
影响因子：
4.6
通讯作者：
Morrisey, Edward E.
中科院分区：
文献类型：
--
作者：
Zhang, Yuzhen;Rath, Nibedita;Morrisey, Edward E.
体外研究表明，加塔和Nkx转录因子家族的成员物理相互作用，并协同激活肺上皮和心脏基因启动子。然而，这种协同作用的相关性尚未在体内得到证实。我们发现Gata 6-Titf 1（Gata 6-Nkx2.1）双杂合（G6-Nkx DH）胚胎和小鼠在肺上皮分化和远端气道发育方面存在严重缺陷，并且磷脂产生减少。G6-Nkx DH胚胎和小鼠中的缺陷与在患有呼吸窘迫综合征（包括支气管肺发育不良）的人类新生儿中观察到的缺陷相似，差异基因表达分析揭示了需要Gata 6和Titf 1（Nkx2.1）协同调控的基本发育途径。这些研究表明，Gata 6和Nkx2.1以协同方式指导体内肺上皮分化和发育，提供了直接证据表明这两个转录因子家族之间的相互作用对于它们共表达的组织的发育至关重要。
In vitro studies have suggested that members of the GATA and Nkx transcription factor families physically interact, and synergistically activate pulmonary epithelial- and cardiac-gene promoters. However, the relevance of this synergy has not been demonstrated in vivo. We show that Gata6-Titf1 (Gata6-Nkx2.1) double heterozygous (G6-Nkx DH) embryos and mice have severe defects in pulmonary epithelial differentiation and distal airway development, as well as reduced phospholipid production. The defects in G6-Nkx DH embryos and mice are similar to those observed in human neonates with respiratory distress syndromes, including bronchopulmonary dysplasia, and differential gene expression analysis reveals essential developmental pathways requiring synergistic regulation by both Gata6 and Titf1 ( Nkx2.1). These studies indicate that Gata6 and Nkx2.1 act in a synergistic manner to direct pulmonary epithelial differentiation and development in vivo, providing direct evidence that interactions between these two transcription factor families are crucial for the development of the tissues in which they are co-expressed.