Partner 4B Ècole Normale Supérieure de Lyon

Our group is located at Ecole Normale Supérieure de Lyon (ENSL), a high-rank institution in France, within the Laboratoire de Biologie Moléculaire de la Cellule. More than 100 researchers focus their work mainly on basic biological questions, on a variety of model systems and have access to several technical facilities. Nuclear receptors are studied by several groups.

Thyroid hormone (TH) is secreted from the thyroid gland and controls a number of functions: body temperature, body growth, small intestine function, brain development etc. It acts directly on gene expression by binding to receptors present in the nucleus of most cell types. Congenital hypothyroidism, usually linked to iodine deficiency, can lead to dwarfism, deafness and severe mental retardation. Thus, if chemicals present in food are able to interfere with TH signalling, they might be dangerous for brain development. Present data are not sufficient to rule out or to confirm such possibility. It is of outmost importance to evaluate the possibility that chemicals studied by CASCADE, can produce irreversible damage to the developing brain in animal models. We use mouse genetics technology to better understand TH signalling in brain and to create reporter systems able to reveal a negative effect of exposure on brain development.

Flamant F, Samarut J: Thyroid hormone receptors:lessons from knockout andknock-in mutant mice Trends Endocrinol Metab. (14) p85-90, 2003.

 

Yen PM, Feng X, Flamant F, Chen Y, Walker RL, Weiss RE, Chassande O, Samarut J, Refetoff S and Meltzer PS:  Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice. EMBO Rep. 4 p581-587, 2003.

 

Dupre, S. M., Guissouma, H., Flamant, F., Seugnet, I., Scanlan, T. S., Baxter, J. D., Samarut, J., Demeneix, B. A., Becker, N: Both TRß1 and TRß2 isoforms contribute to the regulation of hypothalamic TRH. Endocrinology 145, 2337-2345, 2004.

 

Mai W, Janier M, Allioli N, Quignodon L, Cluzel T, Flamant F, Samarut J  Thyroid hormone receptor a is a molecular switch of cardiac function between fetal and postnatal life. Proc Natl Acad Sci USA 101 p10332-7, 2004.

 

Quignodon L, Legrand C, Allioli N, Guanado-Ferraz A, Bernal J, Samarut J, Flamant F: Thyroid hormone sgnaling is highly heterogeneous during pre- and postnatal brain development J Mol Endocrinol. 33 p467-76, 2004.