Roles of the Wnt effector POP-1/TCF in the C. elegans endomesoderm specification gene network.
Roles of the Wnt effector POP-1/TCF in the C. elegans endomesoderm specification gene network.
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Wnt 效应子 POP-1/TCF 在秀丽隐杆线虫内中胚层规范基因网络中的作用。
DOI：
10.1016/j.ydbio.2009.09.042
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发表时间：
2010
影响因子：
2.7
通讯作者：
Maduro,MorrisF
中科院分区：
文献类型：
--
作者：
Owraghi,Melissa;Broitman-Maduro,Gina;Luu,Thomas;Roberson,Heather;Maduro,MorrisF
秀丽隐杆线虫的4细胞期卵裂球是一种内胚层前体细胞。它前面的子代MS主要产生中胚层细胞，而后面的子代E产生整个肠道。MS和E的基因调控网络已经被研究了超过15年。两个细胞特异性的一个关键组成部分是Wnt/β-catenin不对称通路的参与，该通路通过其核效应物POP-1指定MS和E彼此不同。pop-1功能的缺失导致MS被错误地定义为类样细胞，因为pop-1直接抑制MS中的end-1和end-3基因，否则这些基因会促进内胚层的命运。一个长期存在的问题是，除了抑制内胚层命运外，POP-1是否在指定MS命运中起作用。这个问题一直很难问，因为唯一的染色体损伤是去除端-1和端-3的大缺失，去除数百个基因。在这里，我们报道了真正的端-1端-3双突变体的构建。在同时缺乏end-1、end-3和pop-1活性的胚胎中，我们发现MS命运部分恢复，而E表达MS命运的早期标记，并具有MS和c的特征。我们的研究结果表明，pop-1除了抑制内胚层规范外，对MS规范并不重要，并且揭示wnt修饰的pop-1和end-1 /3通过抑制E的MS命运进一步加强E规范。先前的一项研究表明，在相关的C. briggsae线虫中，与Ce-POP-1直接相反，Cb-POP-1不需要抑制MS的内胚层规格，但对e的MS命运的抑制至关重要。本文的研究结果揭示了隐杆线虫内胚层规格组合控制机制的灵活性。
In C. elegans the 4-cell stage blastomere EMS is an endomesodermal precursor. Its anterior daughter, MS, makes primarily mesodermal cells, while its posterior daughter E generates the entire intestine. The gene regulatory network underlying specification of MS and E has been the subject of study for more than 15 years. A key component of the specification of the two cells is the involvement of the Wnt/β-catenin asymmetry pathway, which through its nuclear effector POP-1, specifies MS and E as different from each other. Loss of pop-1 function results in the mis-specification of MS as an E-like cell, because POP-1 directly represses the end-1 and end-3 genes in MS, which would otherwise promote an endoderm fate. A long-standing question has been whether POP-1 plays a role in specifying MS fate beyond repression of endoderm fate. This question has been difficult to ask because the only chromosomal lesions that remove both end-1 and end-3 are large deletions removing hundreds of genes. Here, we report the construction of bona fide end-1 end-3 double mutants. In embryos lacking activity of end-1, end-3 and pop-1 together, we find that MS fate is partially restored, while E expresses early markers of MS fate and adopts characteristics of both MS and C. Our results suggest that POP-1 is not critical for MS specification beyond repression of endoderm specification, and reveal that Wnt-modified POP-1 and END-1/3 further reinforce E specification by repressing MS fate in E. By comparison, a previous work suggested that in the related nematode C. briggsae, Cb-POP-1 is not required to repress endoderm specification in MS, in direct contrast with Ce-POP-1, but is critical for repression of MS fate in E. The findings reported here shed new light on the flexibility of combinatorial control mechanisms in endomesoderm specification in Caenorhabditis.
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