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

作者：Danielsen E Thomas; Moeller Morten E; Yamanaka Naoki; Ou Qiuxiang; Laursen Janne M; Soenderholm Caecilie; Zhuo Ran; Phelps Brian; Tang Kevin; Zeng Jie; Kondo Shu; Nielsen Christian H; Harvald Eva B; Faergeman Nils J; Haley Macy J; O'Connor Kyle A; King Jones Kirst; O'Connor Michael B; Rewitz Kim F^*

来源：Developmental Cell, 2016, 37(6): 558-570.

DOI：10.1016/j.devcel.2016.05.015

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.

• 出版日期2016-6-20