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The Wnt/â-catenin pathway is a key development pathway in metazoans. C. elegans has been extensively used as a model species to study the Wnt pathway. Four â-catenins in C. elegans are important gene expression regulators in Wnt signalling. One of these, bar-1, is part of the canonical Wnt pathway. Together with Wnt effector POP-1, BAR-1 forms a transcription activation complex which regulates the transcription of downstream genes. The effects of bar-1 loss-of-function mutations on many phenotypes, like vulval development and neuronal migration, have been studied well. However, the effects on global gene expression remain largely unknown. The transcriptional profiles of the strain EW15, carrying bar-1(ga80)lof, and Bristol N2 were measured in the L4 stage of age-synchronized populations at 48 hours. Gene expression differences were combines whit ChiP-seq data from the modENCODE project to pinpoint involved transcription factors. Genes differentially expressed between EW15 and N2 showed strong signs that development of bar-1(ga80)lof was slowed down. We verified this observation by measuring the timing of egg-hatching and egg-laying. The development delay increased over time, ranging from 0 hours at the moment of egg-hatching to 6 hours at the moment of the egg laying. After correcting for this development delay, gene expression analysis revealed that the expression of many genes involved in the Wnt pathway were activated in the bar-1 mutant. Furthermore, the genes up-regulated in the bar-1 mutant showed enrichment for transcription factor activity. These up-regulated genes show strong indications of DAG-16 involvement by the combination of modENCODE ChiP-seq data as well as known DAF-16 regulated genes. Together our findings show that bar-1 loss-of-function leads to delayed development and an activated Wnt pathway, and indicate that the DAF-16 stress-response is causative of this development delay.
|Title of host publication||Proceedings of the Berlin C. elegans Meeting 2014|
|Publication status||Published - 2014|
|Event||Berlin C. elegans Meeting 2014, Berlin, Germany - |
Duration: 15 May 2014 → 17 May 2014
|Conference||Berlin C. elegans Meeting 2014, Berlin, Germany|
|Period||15/05/14 → 17/05/14|