van der Bent M Leontien, Sterken Mark G, Volkers Rita J M, Riksen Joost A G, Schmid Tobias, Hajnal Alex, Kammenga Jan E, Snoek L Basten
1] Laboratory of Nematology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands [2].
Laboratory of Nematology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands.
Sci Rep. 2014 May 13;4:4926. doi: 10.1038/srep04926.
C. elegans is extensively used to study the Wnt-pathway and most of the core-signalling components are known. Four β-catenins 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 have been studied well. However, the effects on global gene expression are unknown. Here we report the effects of a loss-of-function mutation bar-1(ga80). By analysing the transcriptome and developmental phenotyping we show that bar-1(ga80) impairs developmental timing. This developmental difference confounds the comparison of the gene expression profile between the mutant and the reference strain. When corrected for this difference it was possible to identify genes that were directly affected by the bar-1 mutation. We show that the Wnt-pathway itself is activated, as well as transcription factors elt-3, pqm-1, mdl-1 and pha-4 and their associated genes. The outcomes imply that this response compensates for the loss of functional bar-1. Altogether we show that bar-1 loss-of function leads to delayed development possibly caused by an induction of a stress response, reflected by daf-16 activated genes.
秀丽隐杆线虫被广泛用于研究Wnt信号通路,并且大多数核心信号成分已为人所知。四种β-连环蛋白是Wnt信号通路中重要的基因表达调节因子。其中之一bar-1是经典Wnt信号通路的一部分。bar-1与Wnt效应因子pop-1一起形成一个转录激活复合体,该复合体调节下游基因的转录。bar-1功能丧失突变对许多表型的影响已得到充分研究。然而,其对全局基因表达的影响尚不清楚。在此我们报告bar-1(ga80)功能丧失突变的影响。通过分析转录组和发育表型,我们发现bar-1(ga80)会损害发育时间。这种发育差异混淆了突变体与参考菌株之间基因表达谱的比较。校正这种差异后,就有可能鉴定出直接受bar-1突变影响的基因。我们发现Wnt信号通路本身被激活,以及转录因子elt-3、pqm-1、mdl-1和pha-4及其相关基因。这些结果表明这种反应补偿了功能性bar-1的缺失。我们总体上表明,bar-1功能丧失导致发育延迟,这可能是由应激反应的诱导引起的,这一点由daf-16激活的基因所反映。