Differential regulation of node formation, nodal ciliogenesis and cilia positioning by Noto and Foxj1

Differential regulation of node formation, nodal ciliogenesis and cilia positioning by Noto and Foxj1
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DOI:
10.1242/dev.072728
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发表时间:
2012-04-01
期刊:
影响因子:
4.6
通讯作者:
Gossler, Achim
Gossler, Achim
中科院分区:
生物学2区
文献类型:
--
作者:
Alten, Leonie;Schuster-Gossler, Karin;Gossler, Achim

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小鼠转录因子 Noto 在节中表达,控制节形态发生、节纤毛的形成和左右不对称。 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 对于小鼠结节纤毛形成的意义尚不清楚。在非羊膜动物中,Foxj1 是相当于节点的结构中纤毛发生所必需的。在这里,我们分析了小鼠胚胎中的节点、节点纤毛和节点流,其中我们用 Foxj1 的编码序列替换了 Noto 编码序列,或者分析了 Foxj1 缺陷的胚胎中的节点、节点纤毛和节点流。我们证明,Noto 基因座表达的 Foxj1 具有功能性,可以在 Noto 缺失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结节上皮平面内的细胞表面上,并且不能恢复正常的结节形态。我们还表明 Foxj1 对于节点中 Rfx3 上游的纤毛发生至关重要。因此,Foxj1 在不对称的脊椎动物器官中的功能是保守的,Noto 独立于 Foxj1 调节节点形态发生和纤毛在节点细胞上的后定位。
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.