The mouse homeobox gene Noto regulates node morphogenesis, notochordal ciliogenesis, and left-right patterning
The mouse homeobox gene Noto regulates node morphogenesis, notochordal ciliogenesis, and left-right patterning
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DOI：
10.1073/pnas.0704344104
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发表时间：
2007-10-02
影响因子：
11.1
通讯作者：
Gossler, Achim
中科院分区：
文献类型：
--
作者：
Beckers, Anja;Alten, Leonie;Gossler, Achim
小鼠同源框基因诺托代表斑马鱼浮头（flh）的同源物，并且在组织者结和新生脊索中表达。先前的分析表明，诺托是脊索尾侧部分形成所必需的。在这里，我们表明，诺托也是必不可少的节点形态，控制纤毛在后脊索，并建立偏侧，而组织者的功能，在前后图案显然没有受到损害。在突变胚胎中，内脏器官的左右不对称和偏侧标记的表达是随机的。突变后脊索区域的大小和形状可变，纤毛缩短与高度不规则的轴丝微管，和基体，部分，位于异常深的细胞质。调节动力蛋白基因Dnahc11的转录因子Foxj1在突变节点中下调，Foxj1是肺上皮细胞中基底体正确锚定所需的。同样，调控纤毛生长的转录因子Rfx 3在诺托突变体中不表达，并且对纤毛功能或组装重要的各种其他基因如Dnahc 5和Nphp 3被下调。我们的研究结果建立诺托作为一个重要的调节节点的形态发生和纤毛发生在后脊索，并建议诺托行为的上游Foxj1和Rfx3。
The mouse homeobox gene Noto represents the homologue of zebrafish floating head (flh) and is expressed in the organizer node and in the nascent notochord. Previous analyses suggested that Noto is required exclusively for the formation of the caudal part of the notochord. Here, we show that Noto is also essential for node morphogenesis, controlling ciliogenesis in the posterior notochord, and the establishment of laterality, whereas organizer functions in anterior-posterior patterning are apparently not compromised. In mutant embryos, left-right asymmetry of internal organs and expression of laterality markers was randomized. Mutant posterior notochord regions were variable in size and shape, cilia were shortened with highly irregular axonemal microtubuli, and basal bodies were, in part, located abnormally deep in the cytoplasm. The transcription factor Foxj1, which regulates the dynein gene Dnahc11 and is required for the correct anchoring of basal bodies in lung epithelial cells, was down-regulated in mutant nodes. Likewise, the transcription factor Rfx3, which regulates cilia growth, was not expressed in Noto mutants, and various other genes important for cilia function or assembly such as Dnahc5 and Nphp3 were down-regulated. Our results establish Noto as an essential regulator of node morphogenesis and ciliogenesis in the posterior notochord, and suggest Noto acts upstream of Foxj1 and Rfx3.