Activated Ras/JNK driven Dilp8 in imaginal discs adversely affects organismal homeostasis during early pupal stage in Drosophila, a new checkpoint for development. Issue 12 (29th August 2019)

• Record Type: Journal Article
• Authors: Ray, Mukulika; Lakhotia, Subhash C.
• Is Part Of: Developmental dynamics. Volume 248:Issue 12(2019)
• Page Start: 1211
• Page End: 1231
• Publication Date: 2019-08-29
• Subjects: ecdysone -- Halloween genes -- hsrω lncRNA -- interorgan signaling -- Ptth; Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.102
• Languages: English
• ISSNs: 1058-8388

Abstract

Abstract: Background: Dilp8‐mediated inhibition of ecdysone synthesis and pupation in holometabolous insects maintains developmental homeostasis through stringent control of timing and strength of molting signals. We examined reasons for normal pupation but early pupal death observed in certain cases. Results: Overexpression of activated Ras in developing eye/wing discs inhibited Ptth expression in brain via upregulated JNK signaling mediated Dilp8 secretion from imaginal discs, which inhibited ecdysone synthesis in prothoracic gland after pupariation, leading to death of ~25‐ to 30‐hour‐old pupae. Inhibition of elevated Ras signaling completely rescued early pupal death while post‐pupation administration of ecdysone to organisms with elevated Ras signaling in eye discs partially rescued their early pupal death. Unlike the earlier known Dilp8 action in delaying pupation, hyperactivated Ras mediated elevation of pJNK signaling in imaginal discs caused Dilp8 secretion after pupariation. Ectopic expression of certain other transgene causing pupal lethality similarly enhanced pJNK and early pupal Dilp8 levels. Suboptimal ecdysone levels after 8 hours of pupation prevented the early pupal metamorphic changes and caused organismal death. Conclusions: Our results reveal early pupal stage as a novel Dilp8 mediated post‐pupariation checkpoint and provide further evidence for interorgan signaling during development, wherein a peripheral tissue influences the CNS driven endocrine function. Key Findings: Ectopic over‐expression of activated Ras using predominantly eye‐ or wing disc specific GAL4 drivers causes early pupal death. Early dying pupae show nether the post‐pupariation metamorphic changes, nor the ecdysone titre surge after 8 Hr of pupation Eye or wing discs over‐expressing activated Ras show very high levels of pJNK and Dilp8, more so after pupariation. The early pupal stage is a novel Dilp8 mediated post‐pupariation checkpoint.