Reciprocal asymmetry of SYS-1/β-catenin and POP-1/TCF controls asymmetric divisions in Caenorhabditis elegans
Reciprocal asymmetry of SYS-1/β-catenin and POP-1/TCF controls asymmetric divisions in Caenorhabditis elegans
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DOI：
10.1073/pnas.0611507104
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发表时间：
2007-02-27
影响因子：
11.1
通讯作者：
Kimble, Judith
中科院分区：
文献类型：
--
作者：
Phillips, Bryan T.;Kidd, Ambrose R., III;Kimble, Judith
β-连环素是后生动物发育的保守调节因子，与TCFDNA结合蛋白一起作用于转录。在秀丽隐杆线虫中，SYS-1/β-catenin和POP-1/Tcf调节几个不对称分裂，包括体细胞性腺前体细胞(SGP)的分裂。在远端而不是近端的Sgp子代中，sys-1/beta-catenin和POP-1/Tcf转录激活CEH-22来指定斜坡的命运。在这里，我们研究了sys-1/β-catenin的分布及其调控。利用一种救助性转基因VNS：：sys-1，它将Venus荧光蛋白与sys-1融合在一起，我们发现远端的VNS：：sys-1比近端的Sgp子代更多，我们将这种现象称为“sys-1不对称”。此外，在许多其他组织中也发现了sys-1的不对称性，这与sys-1在线虫发育过程中广泛调节不对称分裂的观点一致。尤其是，Sys-1在E中比MS中含量更丰富，并且Sys-1对内皮细胞的命运至关重要。在所有情况下，sys-1与POP-1不对称性是相反的：具有较高sys-1的细胞具有较低的POP-1，反之亦然。Sys-1的不对称性是翻译后控制的，依赖于卷曲和蓬乱的同系物，这也控制了POP-1的不对称性。因此，上游调节器通过在同一小区内增加sys-1和减小POP-1来调节sys-1与POP-1的比率。相比之下，SYS-1不对称并不依赖于WRM-1，后者似乎专门用于POP-1不对称。我们提出了一个双管齐下的途径来控制sys-1：POP-1，它可以在不对称的细胞分裂的子代中强有力地完成差异基因的表达。
beta-Catenins are conserved regulators of metazoan development that function with TCF DNA-binding proteins to activate transcription. In Caenorhabditis elegans, SYS-1/beta-catenin and POP-1/TCF regulate several asymmetric divisions, including that of the somatic gonadal precursor cell (SGP). In the distal but not the proximal SGP daughter, SYS-1/beta-catenin and POP-1/TCF transcriptionally activate ceh-22 to specify the clistal fate. Here, we investigate the distribution of SYS-1/beta-catenin and its regulation. Using a rescuing transgene, VNS::SYS-1, which fuses VENUS fluorescent protein to SYS-1, we find more VNS::SYS-1 in distal than proximal SGP daughters, a phenomenon we call "SYS-1 asymmetry." In addition, SYS-1 asymmetry is seen in many other tissues, consistent with the idea that SYS-1 regulates asymmetric divisions broadly during C. elegans development. In particular, SYS-1 is more abundant in E than MS, and SYS-1 is critical for the endodermal fate. In all cases, SYS-1 is reciprocal to POP-1 asymmetry: cells with higher SYS-1 have lower POP-1, and vice versa. SYS-1 asymmetry is controlled posttranslationally and relies on frizzled and dishevelled homologs, which also control POP-1 asymmetry. Therefore, upstream regulators modulate the SYS-1 to POP-1 ratio by increasing SYS-1 and decreasing POP-1 within the same cell. By contrast, SYS-1 asymmetry does not rely on WRM-1, which appears specialized for POP-1 asymmetry. We suggest a two-pronged pathway for control of SYS-1:POP-1, which can robustly accomplish differential gene expression in daughters of an asymmetric cell division.