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Science 309 (5737): 1071-1073

Copyright © 2005 by the American Association for the Advancement of Science

Direct Control of Germline Stem Cell Division and Cyst Growth by Neural Insulin in Drosophila

Leesa LaFever, and Daniela Drummond-Barbosa*

Abstract: Stem cells reside in specialized niches that provide signals required for their maintenance and division. Tissue-extrinsic signals can also modify stem cell activity, although this is poorly understood. Here, we report that neural-derived Drosophila insulin-like peptides (DILPs) directly regulate germline stem cell division rate, demonstrating that signals mediating the ovarian response to nutritional input can modify stem cell activity in a niche-independent manner. We also reveal a crucial direct role of DILPs in controlling germline cyst growth and vitellogenesis.

Department of Cell and Developmental Biology, Vanderbilt University Medical Center, 4120B Medical Research Building III, 465 21st Avenue South, Nashville, TN 37232–8240, USA.

* To whom correspondence should be addressed. E-mail: daniela.drummond-barbosa{at}

Neprilysins: An Evolutionarily Conserved Family of Metalloproteases That Play Important Roles in Reproduction in Drosophila.
J. L. Sitnik, C. Francis, K. Hens, R. Huybrechts, M. F. Wolfner, and P. Callaerts (2014)
Genetics 196, 781-797
   Abstract »    Full Text »    PDF »
Nutritional regulation of stem and progenitor cells in Drosophila.
J. Shim, S. Gururaja-Rao, and U. Banerjee (2013)
Development 140, 4647-4656
   Abstract »    Full Text »    PDF »
Insulin and Target of rapamycin signaling orchestrate the development of ovarian niche-stem cell units in Drosophila.
D. Gancz and L. Gilboa (2013)
Development 140, 4145-4154
   Abstract »    Full Text »    PDF »
Stem cell metabolism in tissue development and aging.
N. Shyh-Chang, G. Q. Daley, and L. C. Cantley (2013)
Development 140, 2535-2547
   Abstract »    Full Text »    PDF »
Receptor Tyrosine Kinases in Drosophila Development.
R. Sopko and N. Perrimon (2013)
Cold Spring Harb Perspect Biol 5, a009050
   Abstract »    Full Text »    PDF »
Diet controls Drosophila follicle stem cell proliferation via Hedgehog sequestration and release.
T. R. Hartman, T. I. Strochlic, Y. Ji, D. Zinshteyn, and A. M. O'Reilly (2013)
J. Cell Biol. 201, 741-757
   Abstract »    Full Text »    PDF »
The Nucleus- and Endoplasmic Reticulum-Targeted Forms of Protein Tyrosine Phosphatase 61F Regulate Drosophila Growth, Life Span, and Fecundity.
B. J. Buszard, T. K. Johnson, T.-C. Meng, R. Burke, C. G. Warr, and T. Tiganis (2013)
Mol. Cell. Biol. 33, 1345-1356
   Abstract »    Full Text »    PDF »
Centrosome misorientation mediates slowing of the cell cycle under limited nutrient conditions in Drosophila male germline stem cells.
T. M. Roth, C.- Y. A. Chiang, M. Inaba, H. Yuan, V. Salzmann, C. E. Roth, and Y. M. Yamashita (2012)
Mol. Biol. Cell 23, 1524-1532
   Abstract »    Full Text »    PDF »
Modulation of gurken translation by insulin and TOR signaling in Drosophila.
S. B. Ferguson, M. A. Blundon, M. S. Klovstad, and T. Schupbach (2012)
J. Cell Sci. 125, 1407-1419
   Abstract »    Full Text »    PDF »
Wolbachia Enhance Drosophila Stem Cell Proliferation and Target the Germline Stem Cell Niche.
E. M. Fast, M. E. Toomey, K. Panaram, D. Desjardins, E. D. Kolaczyk, and H. M. Frydman (2011)
Science 334, 990-992
   Abstract »    Full Text »    PDF »
Nonautonomous regulation of Drosophila midgut stem cell proliferation by the insulin-signaling pathway.
N. H. Choi, E. Lucchetta, and B. Ohlstein (2011)
PNAS 108, 18702-18707
   Abstract »    Full Text »    PDF »
Germline Stem Cells.
A. Spradling, M. T. Fuller, R. E. Braun, and S. Yoshida (2011)
Cold Spring Harb Perspect Biol 3, a002642
   Abstract »    Full Text »    PDF »
The stem cell niche: lessons from the Drosophila testis.
M. de Cuevas and E. L. Matunis (2011)
Development 138, 2861-2869
   Abstract »    Full Text »    PDF »
Long-term live imaging provides new insight into stem cell regulation and germline-soma coordination in the Drosophila ovary.
L. X. Morris and A. C. Spradling (2011)
Development 138, 2207-2215
   Abstract »    Full Text »    PDF »
Intrinsic and extrinsic mechanisms of oocyte loss.
T. C. Thomson, K. E. Fitzpatrick, and J. Johnson (2010)
Mol. Hum. Reprod. 16, 916-927
   Abstract »    Full Text »    PDF »
Specific roles of Target of rapamycin in the control of stem cells and their progeny in the Drosophila ovary.
L. LaFever, A. Feoktistov, H.-J. Hsu, and D. Drummond-Barbosa (2010)
Development 137, 2117-2126
   Abstract »    Full Text »    PDF »
Evaluating the role of reproductive constraints in ant social evolution.
A. Khila and E. Abouheif (2010)
Phil Trans R Soc B 365, 617-630
   Abstract »    Full Text »    PDF »
Insulin signaling promotes germline proliferation in C. elegans.
D. Michaelson, D. Z. Korta, Y. Capua, and E. J. A. Hubbard (2010)
Development 137, 671-680
   Abstract »    Full Text »    PDF »
Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities.
H. Zhang, J. Liu, C. R. Li, B. Momen, R. A. Kohanski, and L. Pick (2009)
PNAS 106, 19617-19622
   Abstract »    Full Text »    PDF »
stall Encodes an ADAMTS Metalloprotease and Interacts Genetically With Delta in Drosophila Ovarian Follicle Formation.
E. F. Ozdowski, Y. M. Mowery, and C. Cronmiller (2009)
Genetics 183, 1027-1040
   Abstract »    Full Text »    PDF »
Dicer-1-dependent Dacapo suppression acts downstream of Insulin receptor in regulating cell division of Drosophila germline stem cells.
J.-Y. Yu, S. H. Reynolds, S. D. Hatfield, H. R. Shcherbata, K. A. Fischer, E. J. Ward, D. Long, Y. Ding, and H. Ruohola-Baker (2009)
Development 136, 1497-1507
   Abstract »    Full Text »    PDF »
Persistent competition among stem cells and their daughters in the Drosophila ovary germline niche.
C. Rhiner, B. Diaz, M. Portela, J. F. Poyatos, I. Fernandez-Ruiz, J. M. Lopez-Gay, O. Gerlitz, and E. Moreno (2009)
Development 136, 995-1006
   Abstract »    Full Text »    PDF »
Insulin levels control female germline stem cell maintenance via the niche in Drosophila.
H.-J. Hsu and D. Drummond-Barbosa (2009)
PNAS 106, 1117-1121
   Abstract »    Full Text »    PDF »
Stem Cells, Their Niches and the Systemic Environment: An Aging Network.
D. Drummond-Barbosa (2008)
Genetics 180, 1787-1797
   Abstract »    Full Text »    PDF »
Stem Cells and Their Niches: Integrated Units That Maintain Drosophila Tissues.
A.C. Spradling, T. Nystul, D. Lighthouse, L. Morris, D. Fox, R. Cox, T. Tootle, R. Frederick, and A. Skora (2008)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Drosophila germ-line modulation of insulin signaling and lifespan.
T. Flatt, K.-J. Min, C. D'Alterio, E. Villa-Cuesta, J. Cumbers, R. Lehmann, D. L. Jones, and M. Tatar (2008)
PNAS 105, 6368-6373
   Abstract »    Full Text »    PDF »
Stem Cell Niche: Microenvironment and Beyond.
J. Zhang and L. Li (2008)
J. Biol. Chem. 283, 9499-9503
   Full Text »    PDF »
Jak/Stat signalling in niche support cells regulates dpp transcription to control germline stem cell maintenance in the Drosophila ovary.
L. Lopez-Onieva, A. Fernandez-Minan, and A. Gonzalez-Reyes (2008)
Development 135, 533-540
   Abstract »    Full Text »    PDF »
Tumbling, an Interactive Way to Move Forward.
H. Sano, S. Ricardo, and R. Lehmann (2007)
Sci. STKE 2007, pe63
   Abstract »    Full Text »    PDF »
Dissecting muscle and neuronal disorders in a Drosophila model of muscular dystrophy.
H. R. Shcherbata, A. S. Yatsenko, L. Patterson, V. D. Sood, U. Nudel, D. Yaffe, D. Baker, and H. Ruohola-Baker (2007)
EMBO J. 26, 481-493
   Abstract »    Full Text »    PDF »
Natural variation in Drosophila melanogaster diapause due to the insulin-regulated PI3-kinase.
K. D. Williams, M. Busto, M. L. Suster, A. K.-C. So, Y. Ben-Shahar, S. J. Leevers, and M. B. Sokolowski (2006)
PNAS 103, 15911-15915
   Abstract »    Full Text »    PDF »
Mutations that increase the life span of C. elegans inhibit tumor growth..
J. M. Pinkston, D. Garigan, M. Hansen, and C. Kenyon (2006)
Science 313, 971-975
   Abstract »    Full Text »    PDF »

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