Institute for Molecular Biology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany.
Development. 2012 Apr;139(7):1276-84. doi: 10.1242/dev.072728. Epub 2012 Feb 22.
The mouse transcription factor Noto is expressed in the node and controls node morphogenesis, formation of nodal cilia and left-right asymmetry. Noto acts upstream of Foxj1, which regulates ciliogenesis in other mouse tissues. However, the significance of Foxj1 for the formation of cilia in the mouse node is unclear; in non-amniote species Foxj1 is required for ciliogenesis in the structures equivalent to the node. Here, we analyzed nodes, nodal cilia and nodal flow in mouse embryos in which we replaced the Noto-coding sequence with that of Foxj1, or in embryos that were deficient for Foxj1. We show that Foxj1 expressed from the Noto locus is functional and restores the formation of structurally normal motile cilia in the absence of Noto. However, Foxj1 is not sufficient for the correct positioning of cilia on the cell surface within the plane of the nodal epithelium, and cannot restore normal node morphology. We also show that Foxj1 is essential for ciliogenesis upstream of Rfx3 in the node. Thus, the function of Foxj1 in vertebrate organs of asymmetry is conserved, and Noto regulates node morphogenesis and the posterior localization of cilia on node cells independently of Foxj1.
小鼠转录因子 Noto 表达于节点，控制节点形态发生、节点纤毛形成和左右不对称。Noto 作用于 Foxj1 的上游，后者调节其他小鼠组织中的纤毛发生。然而，Foxj1 对于小鼠节点中纤毛形成的意义尚不清楚；在非羊膜动物物种中，Foxj1 对于与节点相当的结构中的纤毛发生是必需的。在这里，我们分析了用 Foxj1 取代 Noto 编码序列的小鼠胚胎中的节点、节点纤毛和节点流，或分析了 Foxj1 缺失的胚胎。我们表明，从 Noto 基因座表达的 Foxj1 是有功能的，并且在没有 Noto 的情况下恢复结构正常的运动纤毛的形成。然而，Foxj1 不足以将纤毛正确定位在节点上皮细胞平面内的细胞表面上，并且不能恢复正常的节点形态。我们还表明，Foxj1 对于节点中 Rfx3 上游的纤毛发生是必需的。因此，Foxj1 在脊椎动物不对称器官中的功能是保守的，Noto 调节节点形态发生和节点细胞上纤毛的后向定位，独立于 Foxj1。
