The Study of Wnt Signaling Effector POP-1/TCF in C. Elegans Early Embryos
| dc.contributor.advisor | Lin, Rueyling | en |
| dc.creator | Lo, Miao-Chia | en |
| dc.date.accessioned | 2010-07-12T18:28:10Z | |
| dc.date.available | 2010-07-12T18:28:10Z | |
| dc.date.issued | 2005-04-29 | |
| dc.description.abstract | In C. elegans embryos, the combined Wnt/MAPK pathway polarizes the founder cell of mesendoderm, EMS blastomere, such that EMS produces two daughters with distinct developmental fates. The posterior daughter E, whose fate is specified by Wnt/MAPK, generates intestinal tissues (endoderm), whereas the anterior daughter MS generates pharynx and muscle cells (mesoderm). The downstream Wnt/MAPK effector POP-1 is asymmetrically localized in the nuclei of A-P sisters including the MS/E pair, with a higher level in the anterior cells. This phenomenon is called POP-1 nuclear asymmetry. The Wnt/MAPK signaling is required for POP-1 nuclear asymmetry. It is believed that POP-1 represses endoderm fate in MS and Wnt/MAPK allows endoderm fate in E by downregulating the nuclear level of POP-1. In this study, the potential mechanisms for POP-1 nuclear asymmetry are presented. POP-1 nuclear asymmetry requires a 14-3-3 protein PAR-5 and at least three POP-1 potential phosphorylation sites for the MAPK LIT-1. LIT-1 activity is required for both POP-1/PAR-5 interaction and phosphorylation of at least two of the three potential LIT-1 sites in vivo. Nuclear export is also required for POP-1 nuclear asymmetry. The nuclear level of LIT-1 is higher in the E blastomere, which is regulated by the upstream kinase and Wnt signaling. All together, I propose that in the E blastomere, Wnt/MAPK signaling promotes PAR-5-mediated nuclear export of POP-1, thereby lowering its nuclear level. In addition to this differential nuclear export mechanism, POP-1 nuclear asymmetry may also be regulated by differential protein degradation. This study also shows that POP-1 functions to activate a Wnt/MAPK-responsive gene, sdz-23, in the E blastomere. This challenged the commonly accepted model of Wnt/MAPK-induced gene expression in E, which is based upon the alleviation of the repressive activity of POP-1. The activation of sdz-23 in E requires the ᭣atenin binding domain of POP-1 and a low nuclear level of POP-1. These results suggest that Wnt/MAPK converts the repressor POP-1 into a transcriptional activator and therefore, the non-canonical Wnt signaling in C. elegans early embryos is found to regulate its downstream effector POP-1 in a more canonical way than previously realized. | en |
| dc.format.digitalOrigin | born digital | en |
| dc.format.medium | Electronic | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.oclc | 60493338 | |
| dc.identifier.uri | https://hdl.handle.net/2152.5/566 | |
| dc.language.iso | en | en |
| dc.subject | Caenorhabditis elegans | en |
| dc.subject | DNA-Binding Proteins | en |
| dc.subject | Mitogen-Activated Protein Kinases | en |
| dc.title | The Study of Wnt Signaling Effector POP-1/TCF in C. Elegans Early Embryos | en |
| dc.type | Thesis | en |
| dc.type.genre | dissertation | en |
| dc.type.material | Text | en |
| thesis.degree.department | Graduate School of Biomedical Sciences | en |
| thesis.degree.discipline | Genetics and Development | en |
| thesis.degree.grantor | UT Southwestern Medical Center | en |
| thesis.degree.level | Doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |