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1 CNRS UMR6543, Institute for Signaling, Developmental Biology and Cancer, Parc Valrose, 06108 Nice Cedex 2, France; Present Address: Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. 2 CNRS UMR6543, Institute for Signaling, Developmental Biology and Cancer, Parc Valrose, 06108 Nice Cedex 2, France. 3 CNRS FRE2852, Université P. et M. Curie, 7 quai St. Bernard, 75252 Paris, France. 4 Institut Pasteur, 25-28 rue du Docteur Roux, 75724 Paris, France.
* To whom correspondence should be addressed.
Pierre Léopold , E-mail: leopold{at}unice.fr
All animals coordinate growth and maturation in order to reachtheir final size and shape. In insects, insulin family moleculescontrol growth and metabolism, while pulses of the steroid 20-hydroxyecdysone(20E) initiate major developmental transitions. We show herethat 20E signaling also negatively controls animal growth ratesby impeding general insulin signaling, involving dFOXO localizationand 4E-BP transcription. We also demonstrate that the larvalfat body, equivalent to the vertebrate liver, is a key relayelement for ecdysone-dependent growth inhibition. This establishesthat ecdysone counteracts the growth-promoting action of insulins,thus forming a humoral regulatory loop that determines organismalsize.
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