The team

- Damien Garrido, PhD student

- Brigitte Maroni, Technician

- Jacques Montagne, Senior scientist, CNRS

- Jean-Philippe Parvy, Associated Professor, Université Pierre et
Marie Curie (Paris 6)

Address and phone number

CNRS-CGM

Avenue de la Terrasse - Bât. 26

91198 GIF-SUR-YVETTE

FRANCE

Phone : 33 (0)1 69 82 32 08

Telecopy : 33(0)1 69 82 43 86

Research themes

In our team, we are using the Drosophila model system to focus on cellular growth (cell masse increase) and lipid metabolism. Cellular growth directly depends on nutrient availability, synthesis of macromolecule and the production of metabolic energy. Hence translational capacity and synthesis of fatty acids are limiting in that process as they constitute functional, structural and storage molecules to sustain anabolism and ATP production. At the level of a whole organism, the growth of each organ is coordinated by systemic regulations mediated by hormonal signaling.

Figure 1
S6K loss-of-function (right) in Drosophila induces growth defects. Most of the homozygous mutants die during larval life; few escapers emerge with a severe developmental delay and a reduction in body size that is essentially due to cell size reduction.

To determine how these processes are integrated at the physiological level of a whole organism, we are investigating (1) the signaling network regulated by nutrients, (2) the production of the steroid hormone ecdysone that controls systemic growth and (3) the metabolism of fatty acids.
The S6Kinase Drosophila homologue (dS6K) is a component of the nutrient responsive pathway, whose mutation results in severe growth defect (Fig. 1). We have identified a novel regulator of dS6K-dependent growth, the nuclear receptor DHR3 previously known to coordinate metamorphosis onset. We are currently working to identify novel negative regulators of dS6K.
Nutrient signaling also controls the synthesis of a peak of the steroid hormone ecdysone that triggers molting and metamorphosis. We are studying the dynamic of ecdysone production and screening for novel actors of ecdysone metabolism.
The enzymes that catalyze fatty acid synthesis are attractive targets for drug therapy to cancers and obesity. To establish a physiological map of fatty acid metabolism, we are currently testing in each Drosophila organ the importance of the enzymes implicated in fatty acid metabolism.

Selected publications (since 1999)

Montagne, J. (2011) More about Cyclin G from flies. Cell Cycle, 10 (8) 1187.

Montagne, J., Lecerf, C., Parvy, J.-P., Bennion, J. M., Radimerski, T., Ruhf,M.-L., Zilbermann, F., Vouilloz, N., Stocker, H., Hafen, E., Kozma, S. C. Thomas, G. (2010) The Nuclear Receptor DHR3 Modulates DS6 Kinase-Dependent Growth in Drosophila. PLOS Genetics, 6, e1000937.

Panic, L., Montagne, J., Cokaric, M. and Volarevic, S. (2007) S6-haploinsufficiency activates the p53 tumor suppressor. Cell Cycle, 6 (1) 20-4.

Montagne J. & G. Thomas (2004) S6K integrates nutrient and mitogen signals to control cell growth. In: Hall M, Raff M, Thomas G (eds) Cell growth: control of cell size. Cold Spring Harbor Monograph Series 42. Cold Spring Harbor Press, 265-298.

Colombani J., S. Raisin, S. Pantalacci, Radimerski T., J. Montagne, & P. Léopold. (2003) A Nutrient Sensor Mechanism Controls Drosophila Growth. Cell 114, 739-749.

Perrin L., C. Benassayag, D. Morello, J. Pradel & J. Montagne (2003) modulo is a target of Myc selectively required for growth of proliferative cells in Drosophila. Mech Dev. 120, 645-655.

Radimerski T., J. Montagne, M. Hemmings-Mieszczak & G. Thomas (2002) dS6K Viability of Drosophila Lacking TSC Tumor Suppressor is Rescued by Reducing dTOR/dS6K Signaling. Genes and Dev. 16, 2627-2632.

Radimerski T., J. Montagne, F. Rintelen, H. Stocker, J. van der Kaay, C. P. Downes, E. Hafen, & G. Thomas (2002) dS6K Regulated Cell Growth is dPKB/dPI3K independent, but requires dPDK1. Nat Cell Biol. 4, 251-255.

Montagne J., T. Radimerski & G. Thomas (2001) Insulin Signaling: Lessons from the Drosophila Tuberous Sclerosis Complex, a Tumor Suppressor. Science's STKE: http://stke.sciencemag.org/cgi/content/full/OC_sigtrans;2001/105/pe36.

Oldham S., Montagne J., T. Radimerski, G. Thomas & Ernst Hafen (2000) Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin. Genes and Dev. 14, 2689-2694.

Montagne J. (2000) Genetic and Molecular Mechanisms of Cell Size Control. Mol. Cell Biol. Res. Commun. 4, 195-202.

Montagne J., M. J. Stewart, H. Stocker, E. Hafen, S. C. Kozma & G. Thomas (1999). Drosophila S6 Kinase: A Regulator of Cell Size. Science 285, 2126-2129.