TY - JOUR T1 - High JNK following Ras/Rpr/Tak1 over-expression in eye discs of <em>Drosophila</em> reduces post-pupariation ecdysone via Dilp8 causing early pupal death JF - bioRxiv DO - 10.1101/049882 SP - 049882 AU - Mukulika Ray AU - Subhash C. Lakhotia Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/12/27/049882.abstract N2 - Elevated JNK activity following predominant over-expression of activated Ras or Reaper or Takl in Drosophila larval eye discs does not delay pupation but reduces post-pupariation ecdysone pulse via elevated Dilp8 and reduced Ptth, which results in early pupal death.Abstract We examined reasons for early pupal death following expression of certain transgenes with predominantly eye-disc specific GMR-GAL4 or sev-GAL4 drivers in Drosophila. The GMR-GAL4 or sev-GAL4 driven expression of UAS-Ras1V12 transgene, producing activated Ras, resulted in early (~25-30Hr after pupa formation, APF) and late pupal death, respectively. Coexpression of UAS-hsrω-RNAi transgene or EP3037 to down or up-regulate the hsrω lncRNAs with sev-GAL4&gt;UAS-Ras 1V12 advanced the death to 25-30Hr APF. The normal 8-12Hr APF ecdysone surge was absent in the early dying pupae. Exogenous ecdysone provided between 8-20Hr APF partially suppressed their early death. Microarray, qRT-PCR and immunostaining revealed substantial increase in some JNK pathway members in late larval eye discs, and of Dilp8 in eye discs, reduced transcripts of ptth in brain lobes and of ecdysone biosynthesis enzymes in prothoracic glands of 8-9Hr old pupae in genotypes that show early pupal death. We propose that the high JNK activity in eye discs of GMR-GAL4&gt;UAS-Ras1V12 and sev-GAL4&gt;UAS-Ras1V12 with altered hsrω transcript levels triggers greater Dilp8 secretion from them soon after pupa formation, which inhibits post-pupal ecdysone synthesis in prothoracic gland, leading to early pupal death. The early pupal death following GMR-GAL4 driven expression of UAS-rpr or UAS-tak1 was also associated with comparable enhanced JNK and Dilp8 signaling in eye discs. This study highlights how mis-regulated signaling in one tissue can have global deleterious consequences through downstream events in other tissues, reemphasizing role of inter organ signaling in life of an organism. ER -