Multiple Wnts redundantly control polarity orientation in Caenorhabditis elegans epithelial stem cells.
Multiple Wnts redundantly control polarity orientation in Caenorhabditis elegans epithelial stem cells.
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DOI：
10.1371/journal.pgen.1002308
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发表时间：
2011-10
期刊：
影响因子：
4.5
通讯作者：
Sawa H
中科院分区：
文献类型：
--
作者：
Yamamoto Y;Takeshita H;Sawa H
在发育过程中，细胞极化往往是协调的，以协调组织的模式和形态发生。然而，外界信号如何同步细胞极化尚不清楚。在秀丽隐杆线虫中，大多数有丝分裂细胞沿前后轴极化，分裂不对称。虽然这一过程是由wnt信号通路调节的，但wnt在细胞极性中的作用仅在少数细胞中得到证实。我们分析了Wnt如何控制细胞极性，使用复合Wnt突变体，包括所有五个Wnt基因突变的动物。我们发现，在五重Wnt突变体中，体细胞性腺前体细胞（sgp）是正确极化和定向的，这表明Wnt对于体细胞性腺前体细胞的极性是必不可少的，而体细胞性腺前体细胞的极性需要来自生殖细胞的信号。因此，来自生殖细胞的信号组织了秀丽隐杆线虫的体细胞性腺。相比之下，在复合而非单一Wnt突变体中，大部分6个seam细胞V1-V6（上皮干细胞）保持其极化，但其极性取向变得随机，表明其受到多个Wnt基因的冗余调控。相反，在三种Wnt受体（LIN-17， MOM-5和CAM-1）的功能被破坏的动物中，干细胞没有极化，并且分裂是对称的，这表明Wnt受体对于产生极性是必不可少的，即使在没有Wnt的情况下它们也能发挥作用。除了V5外，所有的接缝细胞都被表达在细胞前部或后部的单个Wnt基因正确极化。在复合Wnt突变体中，后向表达的Wnt在前区异位表达，反之亦然，挽救了极性缺陷，这提出了两种可能性：一是Wnt允许控制极性取向；第二，Wnt功能是有指导意义的，但它们指定的方向是由表达它们的细胞决定的。我们的结果为理解细胞极性如何通过外部信号协调提供了一个范例。器官的正常功能和发育往往需要整个细胞群的同步极化。人们对细胞如何协调它们的极性知之甚少。一个合理的模型是，单个细胞识别外部信号梯度，定向它们的极性，尽管这还没有在任何生物体中显示出来。特别是，尽管Wnt信号对细胞极化很重要，并且Wnt信号梯度对细胞命运的协调规范很重要，但Wnt在定向细胞极性方面的参与尚不清楚。在秀丽隐杆线虫中，大多数不对称分裂的有丝分裂细胞在相同的前后方向上极化。本研究表明，在一组上皮干细胞中，多个Wnt蛋白冗余地控制细胞极性的正确方向，但不控制极化本身。相反，Wnt受体对于细胞的极化表型是必不可少的。大多数干细胞是由Wnt基因正确定向的，Wnt基因在干细胞的前部或后部表达。令人惊讶的是，Wnt信号可以正确地定向干细胞极性，即使它们的来源从前向后或反之亦然。我们的结果表明Wnt基因定向细胞极性的新机制的存在。
During development, cell polarization is often coordinated to harmonize tissue patterning and morphogenesis. However, how extrinsic signals synchronize cell polarization is not understood. In Caenorhabditis elegans, most mitotic cells are polarized along the anterior-posterior axis and divide asymmetrically. Although this process is regulated by a Wnt-signaling pathway, Wnts functioning in cell polarity have been demonstrated in only a few cells. We analyzed how Wnts control cell polarity, using compound Wnt mutants, including animals with mutations in all five Wnt genes. We found that somatic gonadal precursor cells (SGPs) are properly polarized and oriented in quintuple Wnt mutants, suggesting Wnts are dispensable for the SGPs' polarity, which instead requires signals from the germ cells. Thus, signals from the germ cells organize the C. elegans somatic gonad. In contrast, in compound but not single Wnt mutants, most of the six seam cells, V1–V6 (which are epithelial stem cells), retain their polarization, but their polar orientation becomes random, indicating that it is redundantly regulated by multiple Wnt genes. In contrast, in animals in which the functions of three Wnt receptors (LIN-17, MOM-5, and CAM-1) are disrupted—the stem cells are not polarized and divide symmetrically—suggesting that the Wnt receptors are essential for generating polarity and that they function even in the absence of Wnts. All the seam cells except V5 were polarized properly by a single Wnt gene expressed at the cell's anterior or posterior. The ectopic expression of posteriorly expressed Wnts in an anterior region and vice versa rescued polarity defects in compound Wnt mutants, raising two possibilities: one, Wnts permissively control the orientation of polarity; or two, Wnt functions are instructive, but which orientation they specify is determined by the cells that express them. Our results provide a paradigm for understanding how cell polarity is coordinated by extrinsic signals. Proper functions and development of organs often require the synchronized polarization of entire cell groups. How cells coordinate their polarity is poorly understood. One plausible model is that individual cells recognize extrinsic signal gradients that orient their polarity, although this has not been shown in any organism. In particular, although Wnt signaling is important for cell polarization, and Wnt signal gradients are important for the coordinated specification of cell fates, the Wnts' involvement in orienting cell polarity is unclear. In the nematode Caenorhabditis elegans, most asymmetrically dividing mitotic cells are polarized in the same anterior-posterior orientation. Here we show that multiple Wnt proteins redundantly control the proper orientation of cell polarity, but not for polarization per se, in a group of epithelial stem cells. In contrast, Wnt receptors are indispensable for cells to adopt a polarized phenotype. Most stem cells are properly oriented by Wnt genes that are expressed either at their anterior or posterior side. Surprisingly, Wnt signals can properly orient stem cell polarity, even when their source is changed from anterior to posterior or vice versa. Our results suggest the presence of novel mechanisms by which Wnt genes orient cell polarity.
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影响因子：
64.5
作者：
Inoue, T;Oz, HS;Sternberg, PW
通讯作者：
Sternberg, PW
影响因子：
2.7
作者：
Liu, ZC;Fujii, T;Takagi, S
通讯作者：
Takagi, S
DOI：
10.1038/nrg2125
发表时间：
2007-07
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
19
作者：
Green JL;Kuntz SG;Sternberg PW
通讯作者：
Sternberg PW
影响因子：
2.7
作者：
Gilleard, JS;Shafi, Y;McGhee, JD
通讯作者：
McGhee, JD