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Dev Cell. 2016 Jun 20;37(6):558-70. doi: 10.1016/j.devcel.2016.05.015.

A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing.

Author information

1
Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark.
2
Department of Entomology, University of California, Riverside, Riverside, CA 92521, USA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
3
Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada.
4
Center for Biological Sequence Analysis, DTU Systems Biology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
5
Genetic Strains Research Center, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
6
Department of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, 5230 Odense, Denmark.
7
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
8
Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark. Electronic address: kim.rewitz@bio.ku.dk.

Abstract

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.

PMID:
27326933
PMCID:
PMC4918455
DOI:
10.1016/j.devcel.2016.05.015
[Indexed for MEDLINE]
Free PMC Article

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