Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka 560-0043, Japan
Department of Biological Science and Technology, Graduate School of Industrial Science and Technology, Tokyo University of Science, 125-8585, Japan.
Genetics. 2018 Aug;209(4):1099-1119. doi: 10.1534/genetics.118.300935. Epub 2018 May 31.
Notch signaling plays crucial roles in intercellular communications. In , the () gene, which encodes an evolutionarily conserved multi-pass transmembrane protein, appears to be required to activate Notch signaling in some contexts, especially during neuroblast segregation in the neuroectoderm. Although Pcx has been suggested to contribute to endoplasmic reticulum homeostasis, its functions remain unknown. Here, to elucidate these roles, we performed genetic modifier screens of We found that heterozygotes lacking its maternal contribution exhibit cold-sensitive lethality, which is attributed to a reduction in Notch signaling at decreased temperatures. Using sets of deletions that uncover most of the second and third chromosomes, we identified four enhancers and two suppressors of the cold-sensitive lethality. Among these, five genes encode known Notch-signaling components: , (), (), (), a member of the () family, and (). We showed that suppresses Dl endocytosis during neuroblast segregation in the neuroectoderm, as family genes reportedly do in the mesoderm for mesectoderm specification. Analyses of , a key regulator of vesicular fusion, suggested a novel role in neuroblast segregation, which is distinct from Nsf2's previously reported role in imaginal tissues. Finally, , which encodes a potential transcription factor, may play a role in Notch signaling during neuroblast segregation. These results reveal new research avenues for Pcx functions and Notch signaling.
Notch 信号通路在细胞间通讯中发挥着至关重要的作用。在 中,编码进化上保守的多跨膜蛋白的 ()基因似乎在某些情况下需要激活 Notch 信号通路,尤其是在神经外胚层的神经母细胞分离过程中。虽然已经提出 Pcx 有助于内质网稳态,但它的功能仍然未知。在这里,为了阐明这些作用,我们对 进行了遗传修饰剂筛选。我们发现,缺失其母源贡献的 杂合子表现出冷敏感致死性,这归因于 Notch 信号在温度降低时的减少。使用揭示第二和第三染色体大部分区域的缺失集,我们确定了 冷敏感致死性的四个增强子和两个抑制剂。其中,五个基因编码已知的 Notch 信号成分:()、()、()、()、()家族的一个成员和 ()。我们表明,在神经外胚层的神经母细胞分离过程中, 抑制 Dl 内吞作用,正如 家族基因在中胚层中对 mesectoderm 特化所做的那样。对关键调节囊泡融合的 分析表明,在神经母细胞分离中存在新的作用,这与 Nsf2 先前在 imaginal 组织中的作用不同。最后,编码潜在转录因子的 可能在神经母细胞分离过程中的 Notch 信号通路中发挥作用。这些结果揭示了 Pcx 功能和 Notch 信号通路的新研究途径。