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Inactivation of Both foxo and reaper Promotes Long-Term Adult Neurogenesis in Drosophila

Siegrist, Sarah E. and Haque, Najm S. and Chen, Chun-Hong and Hay, Bruce A. and Hariharan, Iswar K. (2010) Inactivation of Both foxo and reaper Promotes Long-Term Adult Neurogenesis in Drosophila. Current Biology, 20 (7). pp. 643-648. ISSN 0960-9822. PMCID PMC2862284. doi:10.1016/j.cub.2010.01.060.

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Adult neurogenesis occurs in specific locations in the brains of many animals, including some insects, and relies on mitotic neural stem cells. In mammals, the regenerative capacity of most of the adult nervous system is extremely limited, possibly because of the absence of neural stem cells. Here we show that the absence of adult neurogenesis in Drosophila results from the elimination of neural stem cells (neuroblasts) during development. Prior to their elimination, their growth and proliferation slows because of decreased insulin/PI3 kinase signaling, resulting in nuclear localization of Foxo. These small neuroblasts are typically eliminated by caspase-dependent cell death, and not exclusively by terminal differentiation as has been proposed. Eliminating Foxo, together with inhibition of reaper family proapoptotic genes, promotes long-term survival of neuroblasts and sustains neurogenesis in the adult mushroom body (mb), the center for learning and memory in Drosophila. Foxo likely activates autophagic cell death, because simultaneous inhibition of ATG1 (autophagy-specific gene 1) and apoptosis also promotes long-term mb neuroblast survival. mb neurons generated in adults incorporate into the existing mb neuropil, suggesting that their identity and neuronal pathfinding cues are both intact. Thus, inhibition of the pathways that normally function to eliminate neural stem cells during development enables adult neurogenesis.

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Hay, Bruce A.0000-0002-5486-0482
Additional Information:© 2010 Elsevier B.V. Received 17 November 2009; revised 20 January 2010; accepted 29 January 2010. Published online: March 25, 2010. Available online 25 March 2010. We thank E. Baehrecke, C. Doe, B. Duriano,M. Freeman, K. White, B. Edgar, R. Tjian, the Bloomington Stock Center, the Developmental Studies Hybridoma Bank, and the Drosophila Genomics Resource Center for fly stocks, antibodies, and/or constructs. We thank K. Siller, N. Patel, D. Bilder, A. Gerhold, C. Doe, D. Weisblat, and J. Boone for discussions and/or reading of the manuscript. S.E.S. is a Robert Black Fellow of the Damon Runyon Cancer Research Foundation (DRG-1960-07), and I.K.H. is funded by the National Institutes of Health (RO1 GM61672, RO1 GM85576).
Funding AgencyGrant Number
Damon Runyon Cancer Research FoundationDRG-1960-07
NIHR01 GM61672
NIHRO1 GM85576
Issue or Number:7
PubMed Central ID:PMC2862284
Record Number:CaltechAUTHORS:20100512-160153430
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Official Citation:Sarah E. Siegrist, Najm S. Haque, Chun-Hong Chen, Bruce A. Hay, Iswar K. Hariharan, Inactivation of Both foxo and reaper Promotes Long-Term Adult Neurogenesis in Drosophila, Current Biology, Volume 20, Issue 7, 2010, Pages 643-648, ISSN 0960-9822, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:18279
Deposited By: Tony Diaz
Deposited On:18 May 2010 20:02
Last Modified:08 Nov 2021 23:42

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