Dipartimento di Farmacia e Biotecnologie, Alma Mater Studiorum Università di Bologna, 40126 Bologna, Italy.
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Int J Mol Sci. 2020 Oct 1;21(19):7257. doi: 10.3390/ijms21197257.
Awd, the homologue of metastasis suppressors, plays key roles in many signaling pathways. Mosaic analysis of the null allele showed that loss of gene function blocks Notch signaling and the expression of its target genes including the Wingless (Wg/Wnt1) morphogen. We also showed that RNA interference (RNAi)-mediated silencing () in larval wing disc leads to chromosomal instability (CIN) and to Jun amino-terminal kinases (JNK)-mediated cell death. Here we show that this cell death is independent of p53 activity. Based on our previous finding showing that forced survival of -CIN cells leads to aneuploidy without the hyperproliferative effect, we investigated the Wg expression in wing disc cells. Interestingly, the Wg protein is expressed in its correct dorso-ventral domain but shows an altered cellular distribution which impairs its signaling. Further, we show that RNAi-mediated knock down of in wing discs does not affect Notch signaling. Thus, our analysis of the hypomorphic phenotype arising from downregulation uncovers a dose-dependent effect of Awd in Notch and Wg signaling.
Awd 是转移抑制因子的同源物,在许多信号通路中发挥关键作用。缺失突变体的镶嵌分析表明,基因功能丧失会阻断 Notch 信号转导及其靶基因的表达,包括 Wingless(Wg/Wnt1)形态发生素。我们还表明,幼虫翅盘中的 RNA 干扰(RNAi)介导的沉默()导致染色体不稳定性(CIN)和 Jun 氨基末端激酶(JNK)介导的细胞死亡。在这里,我们表明这种细胞死亡不依赖于 p53 活性。基于我们之前的发现,即强制存活 -CIN 细胞会导致非整倍体而没有过度增殖的影响,我们研究了 Wg 在 翅盘细胞中的表达。有趣的是,Wg 蛋白在其正确的背腹域表达,但表现出改变的细胞分布,从而损害其信号转导。此外,我们表明,翅盘中的 RNAi 介导的沉默不会影响 Notch 信号转导。因此,我们对由 下调引起的下位表型的分析揭示了 Awd 在 Notch 和 Wg 信号转导中的剂量依赖性作用。