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

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftDevelopmental Cell
Vol/bind37
Udgave nummer6
Sider (fra-til)558-570
Antal sider13
ISSN1534-5807
DOI
StatusUdgivet - 20. jun. 2016

Fingeraftryk

Steroid hormones
Genes
Cholesterol
Hormones
Nutrition
RNA Interference
Chemical activation
Steroids
Feedback
Substrates
Growth

Citer dette

Danielsen, E. T., Moeller, M. E., Yamanaka, N., Ou, Q., Laursen, J. M., Soenderholm, C., ... Rewitz, K. F. (2016). A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing. Developmental Cell, 37(6), 558-570. https://doi.org/10.1016/j.devcel.2016.05.015
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. / A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing. I: Developmental Cell. 2016 ; Bind 37, Nr. 6. s. 558-570.
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title = "A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing",
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.",
author = "Danielsen, {E Thomas} and Moeller, {Morten E} and Naoki Yamanaka and Qiuxiang Ou and Laursen, {Janne M} and Caecilie Soenderholm and Ran Zhuo and Brian Phelps and Kevin Tang and Jie Zeng and Shu Kondo and Nielsen, {Christian H} and Harvald, {Eva B} and Faergeman, {Nils J} and Haley, {Macy J} and O'Connor, {Kyle A} and Kirst King-Jones and O'Connor, {Michael B} and Rewitz, {Kim F}",
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year = "2016",
month = "6",
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Danielsen, ET, Moeller, ME, Yamanaka, N, Ou, Q, Laursen, JM, Soenderholm, C, Zhuo, R, Phelps, B, Tang, K, Zeng, J, Kondo, S, Nielsen, CH, Harvald, EB, Faergeman, NJ, Haley, MJ, O'Connor, KA, King-Jones, K, O'Connor, MB & Rewitz, KF 2016, 'A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing', Developmental Cell, bind 37, nr. 6, s. 558-570. https://doi.org/10.1016/j.devcel.2016.05.015

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

I: Developmental Cell, Bind 37, Nr. 6, 20.06.2016, s. 558-570.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - A Drosophila Genome-Wide Screen Identifies Regulators of Steroid Hormone Production and Developmental Timing

AU - Danielsen, E Thomas

AU - Moeller, Morten E

AU - Yamanaka, Naoki

AU - Ou, Qiuxiang

AU - Laursen, Janne M

AU - Soenderholm, Caecilie

AU - Zhuo, Ran

AU - Phelps, Brian

AU - Tang, Kevin

AU - Zeng, Jie

AU - Kondo, Shu

AU - Nielsen, Christian H

AU - Harvald, Eva B

AU - Faergeman, Nils J

AU - Haley, Macy J

AU - O'Connor, Kyle A

AU - King-Jones, Kirst

AU - O'Connor, Michael B

AU - Rewitz, Kim F

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/6/20

Y1 - 2016/6/20

N2 - 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.

AB - 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.

U2 - 10.1016/j.devcel.2016.05.015

DO - 10.1016/j.devcel.2016.05.015

M3 - Journal article

VL - 37

SP - 558

EP - 570

JO - Developmental Cell

JF - Developmental Cell

SN - 1534-5807

IS - 6

ER -