Reciprocal asymmetry of SYS-1/β-catenin and POP-1/TCF controls asymmetric divisions in Caenorhabditis elegans

Abstract

␤-Catenins are conserved regulators of metazoan development that function with TCF DNA-binding proteins to activate transcription. In Caenorhabditis elegans, SYS-1/␤-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/␤-catenin and POP-1/TCF transcriptionally activate ceh-22 to specify the distal fate. Here, we investigate the distribution of SYS-1/␤-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.dishevelled ͉ frizzled ͉ Wnt/MAPK signaling ͉ asymmetric cell division

The benefits of local depletion: The centrosome as a scaffold for ubiquitin-proteasome-mediated degradation

“…3 SYS-1/b-catenin is a transcription factor acting downstream of the Wnt signaling pathway to activate target genes necessary for cell fate specification. [75][76][77][78][79][80][81][82] During asymmetric division, SYS-1 is targeted to mitotic centrosomes by its interaction with the centrosomal protein RSA-2. 83 Disrupting SYS-1 centrosomal localization by depletion of RSA-2 leads to increased SYS-1 retention by daughter cells after division, indicating the presence of a negative regulatory mechanism involving centrosomal targeting.…”

-Catenin-Dependent Wnt Signaling in C. elegans: Teaching an Old Dog a New Trick

“…The subsequent phosphorylation of POP-1 marks it for nuclear export by PAR-5/14-3-3 and CRM-1/ Exportin (Rocheleau et al 1997;Meneghini et al 1999;Shin et al 1999;Lo et al 2004), leading to a lowering of POP-1/TCF levels in the nucleus of the signaled cell (Lin et al 1998;Meneghini et al 1999;Rocheleau et al 1999;Herman 2001;Maduro et al 2002;Park and Priess 2003;Siegfried et al 2004;Huang et al 2007;Phillips et al 2007). Although the mechanism is unclear, in this daughter cell there is also a Wnt-induced increase in the levels of the b-catenin SYS-1 in the nucleus (Huang et al 2007;Phillips et al 2007). The end result of these Wnt-induced events is an asymmetric distribution of TCF and b-catenin between sister cell nuclei (Fig.…”

“…Forward and reverse genetic screens identified components of Wnt, MAPK, and Src signaling pathways as being required for endoderm formation (Lin et al 1995;Kaletta et al 1997;Rocheleau et al 1997Rocheleau et al , 1999Meneghini et al 1999;Peters et al 1999;Schlesinger et al 1999;Shin et al 1999;Bei et al 2002;Thorpe and Moon 2004;Walston et al 2004;Huang et al 2007;Phillips et al 2007). Wnt pathway components functioning in endoderm induction include MOM-1/Porcupine, MOM-2/Wnt, MIG-14/ Wntless (a.k.a.…”

p21-Activated kinase interacts with Wnt signaling to regulate tissue polarity and gene expression

“…*All animals exhibiting wild-type morphology expressed egl-17::gfp in the wild-type pattern except for one lin-17 ayIs4; ced-10(n1993) mutant, which did not express egl-17::gfp in any P7.p-derived cell. Localization of VNS::SYS-1 was determined using the qIs95 transgene (6,34). Because the expression level is low, we captured images using half-second exposures.…”