Department of Developmental Biology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Dev Biol. 2013 Aug 15;380(2):222-32. doi: 10.1016/j.ydbio.2013.05.011. Epub 2013 May 21.
The node triggers formation of the left-right axis in mouse embryos by establishing local asymmetry of Nodal and Cerl2 expression. We found that Wnt3 is expressed in perinodal crown cells preferentially on the left side. The enhancer responsible for Wnt3 expression was identified and found to be regulated by Foxa2 and Rbpj under the control of Notch signaling. Rbpj binding sites suppress enhancer activity in pit cells of the node, thereby ensuring crown cell-specific expression. In addition, we found that the expression of Gdf1 and Cerl2 is also regulated by Notch signaling, suggesting that such signaling may induce the expression of genes related to left-right asymmetry as a set. Furthermore, Cerl2 expression became symmetric in response to inhibition of Wnt-β-catenin signaling. Our results suggest that Wnt signaling regulates the asymmetry of Cerl2 expression, which likely generates a left-right difference in Nodal activity at the node for further amplification in lateral plate mesoderm.
该节点通过建立 Nodal 和 Cerl2 表达的局部不对称性来触发小鼠胚胎的左右轴形成。我们发现 Wnt3 在旁节点冠细胞中优先表达于左侧。鉴定出负责 Wnt3 表达的增强子，并发现其受 Foxa2 和 Rbpj 的调控，受 Notch 信号的控制。Rbpj 结合位点抑制节点中 pit 细胞的增强子活性，从而确保冠细胞特异性表达。此外，我们发现 Gdf1 和 Cerl2 的表达也受 Notch 信号的调控，表明这种信号可能作为一个整体诱导与左右不对称相关的基因表达。此外，Cerl2 的表达在抑制 Wnt-β-catenin 信号后变得对称。我们的结果表明，Wnt 信号调节 Cerl2 表达的不对称性，这可能在节点中产生 Nodal 活性的左右差异，以便在侧板中进一步放大。
