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Dev Cell. 2017 Aug 21;42(4):363-375.e4. doi: 10.1016/j.devcel.2017.07.020.

Spatial Activation of TORC1 Is Regulated by Hedgehog and E2F1 Signaling in the Drosophila Eye.

Author information

1
National Creative Research Initiatives Center for Energy Homeostasis Regulation and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Republic of Korea.
2
National Creative Research Initiatives Center for Energy Homeostasis Regulation and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Republic of Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.
3
National Creative Research Initiatives Center for Energy Homeostasis Regulation and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 08826, Republic of Korea; School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: jkc@snu.ac.kr.

Abstract

Target of rapamycin complex 1 (TORC1) regulates cell growth in response to nutrients and growth factors. Although TORC1 signaling has been thoroughly studied at the cellular level, the regulation of TORC1 in multicellular tissues and organs has remained elusive. Here we found that TORC1 is selectively activated in the second mitotic wave (SMW), the terminal synchronous cell division, of the developing Drosophila eye. We demonstrated that Hedgehog (Hh) signaling regulates TORC1 through E2F1 and the cyclin D/Cdk4 complex in the SMW, and this regulation is independent from insulin and amino acid signaling pathways. TORC1 is necessary for the proper G1/S transition of the cells, and the activation of TORC1 rescues the cell-cycle defect of Hh signaling-deficient cells in the SMW. Based on this evolutionarily conserved regulation of TORC1 by Hh signaling, we propose that Hh-dependent developmental signaling pathways spatially regulate TORC1 activity in multicellular organisms.

KEYWORDS:

Drosophila TORC1; E2F1; Hedgehog; S6K; cell cycle

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PMID:
28829944
DOI:
10.1016/j.devcel.2017.07.020
[Indexed for MEDLINE]
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