Asahina Masako, Valenta Tomas, Silhankova Marie, Korinek Vladimir, Jindra Marek
Biology Center, Czech Academy of Sciences, University of South Bohemia, Budweis 37005, Czech Republic.
Dev Cell. 2006 Aug;11(2):203-11. doi: 10.1016/j.devcel.2006.06.003.
beta-Catenin signaling determines the proximal-distal axis of the C. elegans gonad by promoting distal fate in asymmetrically dividing somatic gonad precursor cells (SGPs). Impaired function of the Wnt effector POP-1/TCF, its coactivator SYS-1/beta-catenin, and of upstream components including beta-catenin WRM-1 causes all SGP daughters to adopt the proximal fate. Consequently, no distal tip cells (DTCs) that would lead differentiation of gonad arms form in the affected hermaphrodites. Here, we show that deficiency of the nuclear receptor NHR-25 has the opposite effect: extra DTCs develop instead of proximal cells. NHR-25 knockdown restores DTC formation and fertility in pop-1 and sys-1 mutants, suggesting that a balance between NHR-25 and beta-catenin pathway activities is required to establish both proximal and distal fates. This balance relies on direct crossregulation between NHR-25 and the distinct beta-catenin proteins WRM-1 and SYS-1. The nuclear receptor-beta-catenin interaction may be an ancient mechanism of cell-fate decision.
β-连环蛋白信号通路通过促进不对称分裂的体细胞性腺前体细胞(SGP)的远端命运来决定秀丽隐杆线虫性腺的近-远轴。Wnt效应因子POP-1/TCF、其共激活因子SYS-1/β-连环蛋白以及包括β-连环蛋白WRM-1在内的上游成分功能受损,会导致所有SGP子代细胞采用近端命运。因此,在受影响的雌雄同体中,不会形成引导性腺臂分化的远端尖端细胞(DTC)。在这里,我们表明核受体NHR-25的缺乏具有相反的效果:发育出额外的DTC而不是近端细胞。敲低NHR-25可恢复pop-1和sys-1突变体中的DTC形成和生育能力,这表明建立近端和远端命运需要NHR-25和β-连环蛋白信号通路活性之间的平衡。这种平衡依赖于NHR-25与不同的β-连环蛋白WRM-1和SYS-1之间的直接相互调节。核受体与β-连环蛋白的相互作用可能是一种古老的细胞命运决定机制。