A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing
| Autor: | Naoki Yamanaka, Kirst King-Jones, Qiuxiang Ou, Kyle A O'Connor, Jie Zeng, Morten E. Moeller, Janne Marie Laursen, Christian Nielsen, Brian Phelps, Nils J. Færgeman, Kevin Tang, Macy J. Haley, Michael B. O'Connor, Kim F. Rewitz, Eva Bang Harvald, Shu Kondo, Caecilie Soenderholm, Ran Zhuo, E. Thomas Danielsen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Time Factors medicine.medical_treatment Genome Insect Medical and Health Sciences Genome RNA interference Drosophila Proteins Genetics Biological Sciences Phenotype Cholesterol Drosophila melanogaster RNA Interference Steroids Intracellular Biotechnology Signal Transduction Ecdysone Fatty Acid Elongases 1.1 Normal biological development and functioning Embryonic Development Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Underpinning research Acetyltransferases Autophagy medicine Animals Genetic Testing Molecular Biology Gene Metabolic and endocrine Sphingolipids Mechanism (biology) Human Genome Biological Transport Cell Biology Lipid Metabolism Hormones Steroid hormone 030104 developmental biology Insect Developmental Biology Hormone |
| Zdroj: | Thomas Danielsen, E, E. Møller, M, Yamanaka, N, Ou, Q, Laursen, J M, Soenderholm, C, Zhuo, R, Phelps, B, Tang, K, Zeng, J, Kondo, S, H. Nielsen, C, Harvald, E B, Faergeman, N J, J. Haley, M, A. O'Connor, K, King-Jones, K, B. O'Connor, M & F. Rewitz, K 2016, ' A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing ', Developmental Cell, vol. 37, no. 6, pp. 558-570 . https://doi.org/10.1016/j.devcel.2016.05.015 Danielsen, E T, Moeller, M E, Yamanaka, N, Ou, Q, Laursen, J M, Soenderholm, C, Zhuo, R, Phelps, B, Tang, K, Zeng, J, Kondo, S, Nielsen, C H, Harvald, E B, Faergeman, N J, Haley, M J, O'Connor, K A, King-Jones, K, O'Connor, M B & Rewitz, K F 2016, ' A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing ', Developmental Cell, vol. 37, no. 6, pp. 558-570 . https://doi.org/10.1016/j.devcel.2016.05.015 Developmental cell, vol 37, iss 6 |
| ISSN: | 1534-5807 |
| DOI: | 10.1016/j.devcel.2016.05.015 |
| Popis: | Steroid hormones control important developmental processes and are linked to many diseases. To systematically identify genes and pathways required for steroid production, we performed a Drosophila genome-wide in vivo RNAi screen and identified 1,906 genes with potential roles in steroidogenesis and developmental timing. Here, we use our screen as a resource to identify mechanisms regulating intracellular levels of cholesterol, a substrate for steroidogenesis. We identify a conserved fatty acid elongase that underlies a mechanism that adjusts cholesterol trafficking and steroidogenesis with nutrition and developmental programs. In addition, we demonstrate the existence of an autophagosomal cholesterol mobilization mechanism and show that activation of this system rescues Niemann-Pick type C1 deficiency that causes a disorder characterized by cholesterol accumulation. These cholesterol-trafficking mechanisms are regulated by TOR and feedback signaling that couples steroidogenesis with growth and ensures proper maturation timing. These results reveal genes regulating steroidogenesis during development that likely modulate disease mechanisms. |
| Databáze: | OpenAIRE |
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