Studies on the establishment of the primitive streak region

点击翻译按钮获取中文摘要

Posterior extension of body axis is achieved by sequential addition of more posterior tissues in the primitive streak region, which consists of the node and the primitive streak. We previously found that core element of the node/notochord enhancer of Foxa2 gene drives gene expression specifically in the primitive streak region. Thus, to address the mechanism of establishment of the primitive streak region, we analyzed the regulatory mechanism of the core element. The core element is activated in the Wnt/β-catenin treated P19 cells, and this activation depends on the binding sites for two transcription factors. These binding sites are also essential for the in vivo activity of the node/notochord enhancer. One of the enhancer binding proteins is Tead, and inhibition of Tead activity by Tead-EnR in transgenic mouse embryos resulted in the loss of the notochord. Modulation of Tead activity in zebrafish embryos also altered foxa2 expression in the embryonic shield. These findings suggest that cooperation of Tead and a second factor is the central mechanism of Foxa2 expression in the node, and that this mechanism is evolutionally conserved. Since Tead is expressed widely, expression of the second factor should be restricted to the primitive streak region and this factor and Tead should cooperatively regulate gene expression in the primitive streak region. Tead family consists of four closely related proteins. To reveal the role of individual genes, we made knock out mice. Tead1 ; Tead2 double mutant embryos lack Foxa2 expression, and has defects in posterior body axis extension, suggesting that Tead1/2 play central roles in establishment of the central region.