Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 310 (5748): 667-670

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

Antagonistic Actions of Ecdysone and Insulins Determine Final Size in Drosophila

Julien Colombani,1*{dagger} Laurence Bianchini,1* Sophie Layalle,1* Emilie Pondeville,2 Chantal Dauphin-Villemant,2 Christophe Antoniewski,3 Clément Carré,3 Stéphane Noselli,1 Pierre Léopold1{ddagger}

Abstract: All animals coordinate growth and maturation to reach their final size and shape. In insects, insulin family molecules control growth and metabolism, whereas pulses of the steroid 20-hydroxyecdysone (20E) initiate major developmental transitions. We show that 20E signaling also negatively controls animal growth rates by impeding general insulin signaling involving localization of the transcription factor dFOXO and transcription of the translation inhibitor 4E-BP. We also demonstrate that the larval fat body, equivalent to the vertebrate liver, is a key relay element for ecdysone-dependent growth inhibition. Hence, ecdysone counteracts the growth-promoting action of insulins, thus forming a humoral regulatory loop that determines organismal size.

1 CNRS/University of Nice–Sophia Antipolis, UMR6543, Parc Valrose, 06108 Nice Cedex 2, France.
2 CNRS FRE2852, Université P. et M. Curie, 7 quai St. Bernard, 75252 Paris, France.
3 Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris, France.

* These authors contributed equally to this work.

{dagger} Present address: Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.

{ddagger} To whom correspondence should be addressed. E-mail: leopold{at}

The role of reduced oxygen in the developmental physiology of growth and metamorphosis initiation in Drosophila melanogaster.
V. Callier, A. W. Shingleton, C. S. Brent, S. M. Ghosh, J. Kim, and J. F. Harrison (2013)
J. Exp. Biol. 216, 4334-4340
   Abstract »    Full Text »    PDF »
Dynamic feedback circuits function as a switch for shaping a maturation-inducing steroid pulse in Drosophila.
M. E. Moeller, E. T. Danielsen, R. Herder, M. B. O'Connor, and K. F. Rewitz (2013)
Development 140, 4730-4739
   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 »
Dendritic growth gated by a steroid hormone receptor underlies increases in activity in the developing Drosophila locomotor system.
M. F. Zwart, O. Randlett, J. F. Evers, and M. Landgraf (2013)
PNAS 110, E3878-E3887
   Abstract »    Full Text »    PDF »
FijiWings: An Open Source Toolkit for Semiautomated Morphometric Analysis of Insect Wings.
A. C. Dobens and L. L. Dobens (2013)
g3 3, 1443-1449
   Abstract »    Full Text »    PDF »
Temperature-size rule is mediated by thermal plasticity of critical size in Drosophila melanogaster.
S. M. Ghosh, N. D. Testa, and A. W. Shingleton (2013)
Proc R Soc B 280, 20130174
   Abstract »    Full Text »    PDF »
Drosophila neuroblasts: a model for stem cell biology.
C. C. F. Homem and J. A. Knoblich (2012)
Development 139, 4297-4310
   Abstract »    Full Text »    PDF »
Evolution of foraging behaviour in response to chronic malnutrition in Drosophila melanogaster.
R. K. Vijendravarma, S. Narasimha, and T. J. Kawecki (2012)
Proc R Soc B 279, 3540-3546
   Abstract »    Full Text »    PDF »
Conserved microRNA miR-8 controls body size in response to steroid signaling in Drosophila.
H. Jin, V. N. Kim, and S. Hyun (2012)
Genes & Dev. 26, 1427-1432
   Abstract »    Full Text »    PDF »
How Growth Abnormalities Delay "Puberty" in Drosophila.
I. K. Hariharan (2012)
Science Signaling 5, pe27
   Abstract »    Full Text »    PDF »
APL-1, the Alzheimer's Amyloid Precursor Protein in Caenorhabditis elegans, Modulates Multiple Metabolic Pathways Throughout Development.
C. Y. Ewald, D. A. Raps, and C. Li (2012)
Genetics 191, 493-507
   Abstract »    Full Text »    PDF »
Imaginal Discs Secrete Insulin-Like Peptide 8 to Mediate Plasticity of Growth and Maturation.
A. Garelli, A. M. Gontijo, V. Miguela, E. Caparros, and M. Dominguez (2012)
Science 336, 579-582
   Abstract »    Full Text »    PDF »
Control of target gene specificity during metamorphosis by the steroid response gene E93.
X. Mou, D. M. Duncan, E. H. Baehrecke, and I. Duncan (2012)
PNAS 109, 2949-2954
   Abstract »    Full Text »    PDF »
Drosophila RNA polymerase III repressor Maf1 controls body size and developmental timing by modulating tRNAiMet synthesis and systemic insulin signaling.
E. J. Rideout, L. Marshall, and S. S. Grewal (2012)
PNAS 109, 1139-1144
   Abstract »    Full Text »    PDF »
Juvenile Hormone Regulates Vitellogenin Gene Expression through Insulin-like Peptide Signaling Pathway in the Red Flour Beetle, Tribolium castaneum.
Z. Sheng, J. Xu, H. Bai, F. Zhu, and S. R. Palli (2011)
J. Biol. Chem. 286, 41924-41936
   Abstract »    Full Text »    PDF »
Control of body size by oxygen supply reveals size-dependent and size-independent mechanisms of molting and metamorphosis.
V. Callier and H. F. Nijhout (2011)
PNAS 108, 14664-14669
   Abstract »    Full Text »    PDF »
Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75.
L. Caceres, A. S. Necakov, C. Schwartz, S. Kimber, I. J. H. Roberts, and H. M. Krause (2011)
Genes & Dev. 25, 1476-1485
   Abstract »    Full Text »    PDF »
Genome-Wide Deficiency Mapping of the Regions Responsible for Temporal Canalization of the Developmental Processes of Drosophila melanogaster.
K. H. Takahashi, Y. Okada, and K. Teramura (2011)
J. Hered. 102, 448-457
   Abstract »    Full Text »    PDF »
The Metabotropic Glutamate Receptor Activates the Lipid Kinase PI3K in Drosophila Motor Neurons Through the Calcium/Calmodulin-Dependent Protein Kinase II and the Nonreceptor Tyrosine Protein Kinase DFak.
C. Chun-Jen Lin, J. B. Summerville, E. Howlett, and M. Stern (2011)
Genetics 188, 601-613
   Abstract »    Full Text »    PDF »
Neuroendocrine regulation of Drosophila metamorphosis requires TGF{beta}/Activin signaling.
Y. Y. Gibbens, J. T. Warren, L. I. Gilbert, and M. B. O'Connor (2011)
Development 138, 2693-2703
   Abstract »    Full Text »    PDF »
L. M. Riddiford (2011)
J. Exp. Biol. 214, 1613-1615
   Full Text »    PDF »
Insulin/Insulin-Like Growth Factor Signaling Controls Non-Dauer Developmental Speed in the Nematode Caenorhabditis elegans.
A.-F. Ruaud, I. Katic, and J.-L. Bessereau (2011)
Genetics 187, 337-343
   Abstract »    Full Text »    PDF »
The Cellular and Physiological Mechanism of Wing-Body Scaling in Manduca sexta.
H. F. Nijhout and L. W. Grunert (2010)
Science 330, 1693-1695
   Abstract »    Full Text »    PDF »
Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model.
S. A. Sinenko, T. Hung, T. Moroz, Q.-M. Tran, S. Sidhu, M. D. Cheney, N. A. Speck, and U. Banerjee (2010)
Blood 116, 4612-4620
   Abstract »    Full Text »    PDF »
Survival strategies of a sterol auxotroph.
M. Carvalho, D. Schwudke, J. L. Sampaio, W. Palm, I. Riezman, G. Dey, G. D. Gupta, S. Mayor, H. Riezman, A. Shevchenko, et al. (2010)
Development 137, 3675-3685
   Abstract »    Full Text »    PDF »
20-hydroxyecdysone Reduces Insect Food Consumption Resulting in Fat Body Lipolysis During Molting and Pupation.
S. Wang, S. Liu, H. Liu, J. Wang, S. Zhou, R. J. Jiang, W. G. Bendena, and S. Li (2010)
J Mol Cell Biol 2, 128-138
   Abstract »    Full Text »    PDF »
The Insect Neuropeptide PTTH Activates Receptor Tyrosine Kinase Torso to Initiate Metamorphosis.
K. F. Rewitz, N. Yamanaka, L. I. Gilbert, and M. B. O'Connor (2009)
Science 326, 1403-1405
   Abstract »    Full Text »    PDF »
Schlank, a member of the ceramide synthase family controls growth and body fat in Drosophila.
R. Bauer, A. Voelzmann, B. Breiden, U. Schepers, H. Farwanah, I. Hahn, F. Eckardt, K. Sandhoff, and M. Hoch (2009)
EMBO J. 28, 3706-3716
   Abstract »    Full Text »    PDF »
Infection by a symbiotic polydnavirus induces wasting and inhibits metamorphosis of the moth Pseudoplusia includens.
A. J. Pruijssers, P. Falabella, J. H. Eum, F. Pennacchio, M. R. Brown, and M. R. Strand (2009)
J. Exp. Biol. 212, 2998-3006
   Abstract »    Full Text »    PDF »
The Ecdysone receptor controls the post-critical weight switch to nutrition-independent differentiation in Drosophila wing imaginal discs.
C. K. Mirth, J. W. Truman, and L. M. Riddiford (2009)
Development 136, 2345-2353
   Abstract »    Full Text »    PDF »
Juvenile hormone counteracts the bHLH-PAS transcription factors MET and GCE to prevent caspase-dependent programmed cell death in Drosophila.
Y. Liu, Z. Sheng, H. Liu, D. Wen, Q. He, S. Wang, W. Shao, R.-J. Jiang, S. An, Y. Sun, et al. (2009)
Development 136, 2015-2025
   Abstract »    Full Text »    PDF »
Ecdysone signaling regulates the formation of long-term courtship memory in adult Drosophila melanogaster.
H. Ishimoto, T. Sakai, and T. Kitamoto (2009)
PNAS 106, 6381-6386
   Abstract »    Full Text »    PDF »
Integration of Insulin receptor/Foxo signaling and dMyc activity during muscle growth regulates body size in Drosophila.
F. Demontis and N. Perrimon (2009)
Development 136, 983-993
   Abstract »    Full Text »    PDF »
20-Hydroxyecdysone decreases weight and hyperglycemia in a diet-induced obesity mice model.
P. Kizelsztein, D. Govorko, S. Komarnytsky, A. Evans, Z. Wang, W. T. Cefalu, and I. Raskin (2009)
Am J Physiol Endocrinol Metab 296, E433-E439
   Abstract »    Full Text »    PDF »
Decreased Fetal Size Is Associated With {beta}-Cell Hyperfunction in Early Life and Failure With Age.
M. V. Chakravarthy, Y. Zhu, M. B. Wice, T. Coleman, K. L. Pappan, C. A. Marshall, M. L. McDaniel, and C. F. Semenkovich (2008)
Diabetes 57, 2698-2707
   Abstract »    Full Text »    PDF »
Quantitative Trait Loci Affecting Phenotypic Plasticity and the Allometric Relationship of Ovariole Number and Thorax Length in Drosophila melanogaster.
A. O. Bergland, A. Genissel, S. V. Nuzhdin, and M. Tatar (2008)
Genetics 180, 567-582
   Abstract »    Full Text »    PDF »
Developmental model of static allometry in holometabolous insects.
A. W Shingleton, C. K Mirth, and P. W Bates (2008)
Proc R Soc B 275, 1875-1885
   Abstract »    Full Text »    PDF »
Serotonin and insulin signaling team up to control growth in Drosophila.
A.-F. Ruaud and C. S. Thummel (2008)
Genes & Dev. 22, 1851-1855
   Abstract »    Full Text »    PDF »
A matter of timing: microRNA-controlled temporal identities in worms and flies.
M. Frasch (2008)
Genes & Dev. 22, 1572-1576
   Abstract »    Full Text »    PDF »
microRNA miR-14 acts to modulate a positive autoregulatory loop controlling steroid hormone signaling in Drosophila.
J. Varghese and S. M. Cohen (2007)
Genes & Dev. 21, 2277-2282
   Abstract »    Full Text »    PDF »
On the origin and evolutionary diversification of beetle horns.
D. J. Emlen, L. Corley Lavine, and B. Ewen-Campen (2007)
PNAS 104, 8661-8668
   Abstract »    Full Text »    PDF »
Larval feeding duration affects ecdysteroid levels and nutritional reserves regulating pupal commitment in the yellow fever mosquito Aedes aegypti (Diptera: Culicidae).
A. Telang, L. Frame, and M. R. Brown (2007)
J. Exp. Biol. 210, 854-864
   Abstract »    Full Text »    PDF »
Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons.
J. A. Walker, A. V. Tchoudakova, P. T. McKenney, S. Brill, D. Wu, G. S. Cowley, I. K. Hariharan, and A. Bernards (2006)
Genes & Dev. 20, 3311-3323
   Abstract »    Full Text »    PDF »
Control of Metabolism and Growth Through Insulin-Like Peptides in Drosophila.
C. Geminard, N. Arquier, S. Layalle, M. Bourouis, M. Slaidina, R. Delanoue, M. Bjordal, M. Ohanna, M. Ma, J. Colombani, et al. (2006)
Diabetes 55, S5-S8
   Abstract »    Full Text »    PDF »
Mutation of TweedleD, a member of an unconventional cuticle protein family, alters body shape in Drosophila.
X. Guan, B. W. Middlebrooks, S. Alexander, and S. A. Wasserman (2006)
PNAS 103, 16794-16799
   Abstract »    Full Text »    PDF »
Neverland is an evolutionally conserved Rieske-domain protein that is essential for ecdysone synthesis and insect growth.
T. Yoshiyama, T. Namiki, K. Mita, H. Kataoka, and R. Niwa (2006)
Development 133, 2565-2574
   Abstract »    Full Text »    PDF »
Juvenile hormone is required to couple imaginal disc formation with nutrition in insects..
J. W. Truman, K. Hiruma, J. P. Allee, S. G. B. MacWhinnie, D. T. Champlin, and L. M. Riddiford (2006)
Science 312, 1385-1388
   Abstract »    Full Text »    PDF »
Activation of nicotinic receptors uncouples a developmental timer from the molting timer in C. elegans.
A.-F. Ruaud and J.-L. Bessereau (2006)
Development 133, 2211-2222
   Abstract »    Full Text »    PDF »
DEVELOPMENTAL BIOLOGY: Enhanced: Less Steroids Make Bigger Flies.
K. King-Jones and C. S. Thummel (2005)
Science 310, 630-631
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882