No abstract

Reproduction is an energy-intensive process requiring systemic coordination. However, the inter-organ signaling mechanisms that relay nutrient status to modulate reproductive output are poorly understood. Here, we useDrosophila melanogasteras a model to establish the Integrated Stress Response (ISR) transcription factor, Atf4, as a fat tissue metabolic sensor which instructs oogenesis. We demonstrate that Atf4 regulates the lipase Brummer to mediate yolk lipoprotein synthesis in the fat body. Depletion ofAtf4in the fat body also blunts oogenesis recovery after amino acid deprivation and re-feeding, suggestive of a nutrient sensing role for Atf4. We also discovered that Atf4 promotes secretion of a fat body-derived neuropeptide, CNMamide, which modulates neural circuits that promote egg-laying behavior (ovulation). Thus, we posit that ISR signaling in fat tissue acts as a "metabolic sensor" that instructs female reproduction: directly, by impacting yolk lipoprotein production and follicle maturation, and systemically, by regulating ovulation.

No abstract

Heat shock factor (HSF) is a transcription factor that is activated in response to an accumulation of misfolded proteins in the cytoplasm. In contrast, the unfolded protein response (UPR) is a transcriptional response pathway that responds to the accumulation of misfolded proteins in the endoplasmic reticulum. Both pathways, when activated by misfolded proteins, result in a transcriptional response that helps the cell to survive by making factors to help the cell sequester and destroy the misfolded proteins. Using aseptic techniques, Saccharomyces cerevisiae with UPR or HSF Beta‐galactosidase reporter plasmids were grown and tested with various doses of 4 different chemical stressors (Dithiothreitol, Diamide, Hydrogen Peroxide, Beta‐Mercaptoethanol) that may induce protein misfolding. Beta‐galactosidase assays were completed to determine the transcriptional response of the HSF and UPR pathways to the chemical stressors. Importantly, this activity emphasizes the mechanism of action of two different cell signaling pathway and demonstrates the use of a marker gene to determine transcriptional activity of a pathway. This laboratory exercises engages the student in critical thinking and data analysis skills as they evaluate data to determine if their chemical stressor activated both pathways or only one pathway.