The Study of WNT Signaling Effector POP-1/TCF in c. Elegans Early Embryos

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Title: The Study of WNT Signaling Effector POP-1/TCF in c. Elegans Early Embryos
Author: Lo, Miao-Chia
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 .
URI: http : / /hdl .handle .net /2152 .5 /566
Date: 2005-04-29

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The Study of WNT Signaling Effector POP-1/TCF in c. Elegans Early Embryos. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /566 .

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