Expression of the mouse fgf15 gene is directly initiated by Sonic hedgehog signaling in the diencephalon and midbrain
Expression of the mouse fgf15 gene is directly initiated by Sonic hedgehog signaling in the diencephalon and midbrain
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DOI：
10.1002/dvdy.20236
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发表时间：
2005-02-01
影响因子：
2.5
通讯作者：
Ishibashi, M
中科院分区：
文献类型：
--
作者：
Saitsu, H;Komada, M;Ishibashi, M
Sonic Hedgehog (Shh) 是一种分泌分子，被认为可以调节脊椎动物胚胎中的组织生长和模式。尽管有报道称Gli转录因子介导Shh信号传导至细胞核，但人们对Gli的发育靶基因知之甚少。在之前的遗传学研究中，我们发现Shh是间脑和中脑中Fgt75表达所必需的。在这里，我们检查了 Fgt75 是否是通过 Gli 的 Shh 信号传导的直接目标。到七体节阶段，Shh 在中线细胞中表达，Fgt75 在间脑/中脑的内侧区域表达。 Fgt75表达结构域与Gli1的表达结构域一致，并与Gli2的表达结构域重叠。在七体节Shh突变体胚胎中，间脑/中脑中的Fgt75表达大大降低。转基因分析表明，Fgt75 基因的 3.6-kb 5'-侧翼区域足以在内侧/腹侧间脑/中脑中诱导 Fgt75。荧光素酶测定显示 3.6-kb Fgt75 增强子/启动子被 Gli2 激活。 Gli 结合位点位于转录起始位点上游 1 kb 处，是在转基因胚胎的内侧/腹侧间脑/中脑中表达以及在荧光素酶测定中激活所必需的。这些发现表明 Fgt75 通过 Gli 蛋白直接受到 Shh 信号传导的调节。 (C) 2004 Wiley-Liss, Inc.
Sonic hedgehog (Shh) is a secreted molecule that is thought to regulate tissue growth and patterning in vertebrate embryos. Although it has been reported that Gli transcription factors mediate Shh signaling to the nucleus, little is known about developmental target genes of Gli. In the previous genetic study, we showed that Shh is required for Fgt75 expression in the diencephalon and midbrain. Here, we examined whether Fgt75 is a direct target of Shh signaling through Gli. Shh was expressed in the midline cells and Fgt75 in the medial region of the diencephalon/midbrain by the seven-somite stage. The Fgt75 expression domain coincided with that of Gli1 and overlapped with that of Gli2 at this stage. Fgt75 expression in the diencephalon/midbrain was greatly reduced in the seven-somite Shh mutant embryos. Transgenic analysis showed that the 3.6-kb 5'-flanking region of the Fgt75 gene is sufficient for induction of Fgt75 in the medial/ventral diencephalon/midbrain. Luciferase assay showed that the 3.6-kb Fgt75 enhancer/promoter was activated by Gli2. A Gli-binding site was located 1 kb upstream of the transcription start site and was required for expression in the medial/ventral diencephalon/midbrain in transgenic embryos and for activation in luciferase assay. These findings indicate that Fgt75 is directly regulated by Shh signaling through Gli proteins. (C) 2004 Wiley-Liss, Inc.