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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.  Dev. Cell 37(6): 558--570.
FlyBase ID
FBrf0232696
Publication Type
Research paper
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.

Graphical Abstract
Obtained with permission from Cell Press.
PubMed ID
PubMed Central ID
PMC4918455 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Dev. Cell
    Title
    Developmental Cell
    Publication Year
    2001-
    ISBN/ISSN
    1534-5807 1878-1551
    Data From Reference