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Wnt和Bmp信号协同调节背侧端脑Emx2基因的梯度表达。

Wnt and Bmp signalling cooperatively regulate graded Emx2 expression in the dorsal telencephalon.

作者信息

Theil Thomas, Aydin Songül, Koch Silke, Grotewold Lars, Rüther Ulrich

机构信息

Institute for Animal Developmental and Molecular Biology, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.

出版信息

Development. 2002 Jul;129(13):3045-54. doi: 10.1242/dev.129.13.3045.

Abstract

Pattern formation of the dorsal telencephalon is governed by a regionalisation process that leads to the formation of distinct domains, including the future hippocampus and neocortex. Recent studies have implicated signalling proteins of the Wnt and Bmp gene families as well as several transcription factors, including Gli3 and the Emx homeobox genes, in the molecular control of this process. The regulatory relationships between these genes, however, remain largely unknown. We have used transgenic analysis to investigate the upstream mechanisms for regulation of Emx2 in the dorsal telencephalon. We have identified an enhancer from the mouse Emx2 gene that drives specific expression of a lacZ reporter gene in the dorsal telencephalon. This element contains binding sites for Tcf and Smad proteins, transcriptional mediators of the Wnt and Bmp signalling pathway, respectively. Mutations of these binding sites abolish telencephalic enhancer activity, while ectopic expression of these signalling pathways leads to ectopic activation of the enhancer. These results establish Emx2 as a direct transcriptional target of Wnt and Bmp signalling and provide insights into a genetic hierarchy involving Gli3, Emx2 and Bmp and Wnt genes in the control of dorsal telencephalic development.

摘要

背侧端脑的模式形成受区域化过程的调控,该过程导致不同区域的形成,包括未来的海马体和新皮层。最近的研究表明,Wnt和Bmp基因家族的信号蛋白以及几种转录因子,包括Gli3和Emx同源框基因,参与了这一过程的分子调控。然而,这些基因之间的调控关系在很大程度上仍然未知。我们利用转基因分析来研究背侧端脑中Emx2调控的上游机制。我们从小鼠Emx2基因中鉴定出一个增强子,它驱动lacZ报告基因在背侧端脑中特异性表达。该元件包含Tcf和Smad蛋白的结合位点,分别是Wnt和Bmp信号通路的转录介导因子。这些结合位点的突变消除了端脑增强子的活性,而这些信号通路的异位表达导致增强子的异位激活。这些结果确立了Emx2是Wnt和Bmp信号的直接转录靶点,并为涉及Gli3、Emx2以及Bmp和Wnt基因在背侧端脑发育控制中的遗传层级提供了见解。

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