URA2182 - Genes, Synapses and Cognition

After a Master in the field of plant biology, I obtained my Ph.D in human genetics to study mitochondrial diseases. I studied the fate of mtDNA deletions and identified the first mutations of the Krebs cycle (FH) and of the nuclear genes of the respiratory chain (SDHA) in humans. I obtained a permanent position as Assistant Professor at University Denis Diderot Paris 7 and joined the Institut Pasteur to study the role of the Y chromosome in male infertility.

In 2003, I established a laboratory to study the genetics of autism spectrum disorders (ASD). Our most recent results include the identification of one synaptic pathway associated with ASD. The causative genes code for cell adhesion molecules (NLGN3, NLGN4, NRXN1) or scaffolding protein (SHANK2 and SHANK3), which are crucial factors for appropriate synaptic function. In parallel, we recently identified genetic mutations disrupting melatonin synthesis in individuals with ASD. On the bases of these results, our present projects aim to understand the role of the synaptic and circadian-clock genes in the development of language and social communication in humans.

Selected Publications

Schmeisser MJ*, Ey E*, Wegener S*, Bockmann J, Stempel AV, Kuebler A, Janssen AL, Udvardi PT, Shiban E, Spilker C, Balschun D, Skryabin BV, Dieck ST, Smalla KH, Montag D, Leblond CS, Faure P, Torquet N, Le Sourd AM, Toro R, Grabrucker AM, Shoichet SA, Schmitz D, Kreutz MR, Bourgeron T, Gundelfinger ED, Boeckers TM (2012) Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature, 2012 Apr 29;486(7402):256-60 *equally contributed
Leblond C S, Heinrich J, Delorme R, Proepper C, Betancur C, Huguet G, Konyukh M, Chaste P, Ey E, Rastam M, Anckarsäter H, Nygren G, Gillberg I C, Melke J, Toro R, Regnault B, Fauchereau F, Mercati O, Lemière N, Skuse D, Poot M, Holt R, Monaco A P, Järvelä I, Kantojärvi K, Vanhala R, Curran S, Collier D A, Bolton P, Chiocchetti A, Klauck S M, Poustka F, Freitag C M, Waltes R, Kopp M, Duketis E, Bacchelli E, Minopoli F, Ruta L, Battaglia A, Mazzone L, Maestrini E, Sequeira A F, Oliveira B, Vicente A, Oliveira G, Pinto D, Scherer S W, Zelenika D, Delepine M, Lathrop M, Bonneau D, Guinchat V, Devillard F, Assouline B, Mouren M-C, Leboyer M, Gillberg C, Boeckers T M, Bourgeron T (2012) Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. PLoS Genetics 8(2): 1-17
Pinto D et al (2010) Functional impact of global rare copy number variation in autism. Nature 466 : 368-72.
Jamain S., Radyushkin K, Hammerschmidt K, Granon S, Boretius S, Varoqueaux F, Ramanantsoa N, Gallego J, Ronnenberg A, Winter D, Frahm J, Fischer J, Bourgeron T, Ehrenreich H, and Brose N (2008) Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism. Proc Natl Acad Sci U S A. 105:1710-1715.
Melke J, Goubran-Botros H, Chaste P, Betancur C, Nygren G, AnckarsäterH, Rastam M, Ståhlberg O, Gillberg IC, Delorme R, Chabane N, Mouren-Simeoni MC, Fauchereau F, Durand CM, Chevalier F, Drouot X, Collet C, Launay JM, Leboyer M, Gillberg C, and Bourgeron T (2008) Abnormal Melatonin Synthesis in Autism Spectrum Disorders. Molecular Psychiatry 13:90-98.
Szatmari P et al (2007) Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nature Genetics 39:319-28.
Durand C, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, Nygren G, Rastam M, Gillberg IC, Anckarsäter H, Sponheim E, Goubran-Botros H, Delorme R, Chabane N, Mouren-Simeoni MC, de Mas P, Bieth E, Rogé B, Héron D, Burglen L, Gillberg C, Leboyer M, Bourgeron T (2007) Mutations of the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nature Genetics 39:25-7.
Jamain S, Quach H, Betancur C, Råstam M, Colineaux C, Gillberg IC, Soderstrom H, Giros B, Leboyer M, Gillberg C, Bourgeron T and the Paris study (2003) Mutations of the X-linked neuroligins NLGN3 and NLGN4 are associated with autism. Nature Genetics 34, 27-29.
Toro R, Konyukh M, Delorme R, Leblond C, Chaste P, Fauchereau F, Coleman M, Leboyer M, Gillberg C and Bourgeron T (2010) Key role for gene dosage and synaptic homeostasis in autism spectrum disorders. Trends in Genetics 26:363-372.
Bourgeron T (2009) A synaptic trek to autism. Curr. Opin. Neurobiol 19:1-4.
Bourgeron T (2007) The Possible Interplay of Synaptic and Clock Genes in Autism Spectrum Disorders. Cold Spring Harb Symp Quant Biol 72:645-54.
Belmonte MK and Bourgeron T (2006) Fragile X Syndrome and Autism at the Intersection of Genetic and Neuronal Networks. Nature Neuroscience 9:1221-1225.
Persico A. and Bourgeron T (2006) Searching for ways out of the autism maze: Genetic, epigenetic, and environmental clues. Trends in Neurosience 29, 349-358.

Contact

e-mail:	thomasb@pasteur.fr
phone:	(33) 1 40 61 32 16
fax:	(33) 1 45 68 83 69