Localized Depletion of Drosophila Upf1 and Upf2 in the Central Nervous System Leading to Anatomical Defects of the CNS of the Embryo and Larva

[摘要] Nonsense-mediated mRNA decay (NMD) is a quality control pathway that degrades mRNAs with premature termination codons, (PTC), which otherwise will result into a truncated protein with a potential dominant-negative effect. NMD is also an RNA turnover regulatory mechanism for controlling a significant percentage of wild type mRNAs. The pathway functions via coordination of some proteins known as NMD factors. The core NMD factors are Upf1, Upf2, and Upf3, which, in coordination with other important factors tag and mobilize an mRNA for degradation. The role of NMD in the architectural development of central nervous system (CNS) in different organisms has been studied. However, these in vivo studies of the involvement of NMD presented some challenges due to the lethality of Upf1 and Upf2. In this work, we studied the CNS localized loss of function and considered the effect of depletion of Upf1, Upf2, and Upf3 at an early and late Drosophila embryogenesis on the overall anatomical structures of the CNS in the embryo and the larvae. We found that depletion of Upf1 and Upf2 at early embryogenesis caused a significant reduction in the hatching and viability of the embryos. Also, the area of the ventral nerve cord in relation to the total area of the embryo was significantly reduced. However, the Upf3 depleted embryos exhibited normal hatching rates, viability, and ventral nerve cord area when compared with the control. Additionally, CNS localized depletion of Upf1 and Upf2 but not Upf3 at the late stage of embryogenesis resulted in the reduction of the optic lobe of the third instar larval brain. Our findings suggest that NMD factors Upf1 and Upf2 are necessary during the early and late Drosophila CNS development. Their absence in the CNS interferes with its developmental processes.

[学科分类] 生物科学（综合）

[关键词] Nonsense-mediated mRNA decay;NMD factors;Central nervous system;Drosophila melanogaster;Embryogenesis