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Institutes/ Institute of biology technologies - Saclay (IBITEC-S)/ Department of Integrative Biology and Molecular Genetics (SBiGeM)/ Physiogenomics laboratory (LPG)/ Neuro transcriptomes and paleogenetic (JM. Elalouf)

Neuro transcriptomes and paleogenetic

Jean-Marc ELALOUF
CEA Saclay/Bât. 144

Tél : 01 69 08 80 22
jean-marc.elalouf@cea.fr


iBiTec-S / SBIGeM / LPG


Human resources
Michel de CHALDÉE, Researcher
Jean-Marc ELALOUF, Group Leader
Véronique BERTHONAUD, Technicienne Supérieure
Céline BON, PhD Student
Na'a LEPEIJOVA, PhD Student


Research Programs

Theme 1 : Post-genomic analysis of brain regions.

The mammalian brain, sometimes considered the most complex structure in the universe, is composed of multiple regions defined by their anatomical and functional characteristics. In order to acquire molecular data on such a great number of regions, we have analyzed their transcriptome. A micromethod derived from the SAGE technique (Serial Analysis of Gene Expression) was applied to eleven brain regions, in particular different cortical regions, the striatum (caudate nucleus and putamen), the thalamus and the substantia nigra. Among one million cDNA fragments, we have identified several hundred transcripts displaying a heterogeneous distribution in the mouse brain. We have also studied the expression of a subset of these transcripts in the human brain, and identified regional markers that display a similar expression pattern in both species.

The discovery of capucine (Tmem90a), a gene characterized in our laboratory, is a representative example of some outcomes for our transcriptome analysis. The capucine mRNA is mainly detected in the striatum of mice and humans. We have shown a sharp decrease of capucine expression in murine models of Huntington disease, a neurodegenerative illness which affects mainly the caudate nucleus. This observation led us to study the transcript markers for the brain regions affected by Huntington and Parkinson diseases in animal models. Alterations of expression were demonstrated for several regional markers.

Our post-genomic analyses are now focused on characterizing new coding and non-coding transcripts of unknown functions that are expressed in defined brain regions.

With regard to coding transcripts, our study is complemented by the localization of the encoded proteins, recently initiated by the LC-MS/MS analysis of different brain regions. Secreted proteins are evidenced through mass spectrometry analysis of the extracellular fluid collected using in vivo microdialysis.

                                 
                                                         ©CEA/C Brochier


Theme 2 : Paleogenetics of the fauna from the Chauvet-Pont d’Arc Cave

Our laboratory is involved in the multidisciplinary research project carried out in the Chauve-Pont d’Arc Cave, which contains the oldest human paintings ever found, dated back to 32,000 years before present. We are responsible for the molecular analysis of the Pleistocene fauna, particularly abundant in this cave because of its exceptional preservation, and prolonged use by the cave bear. Other species, such as canidae or ibex, are less frequently encountered.

To evaluate the preservation of organic matter in animal remains, we analyze the extent of amino acids racemization. Radiocarbon dating is performed through a collaborative approach with other teams of the project. The overall purpose of our studies is to characterize the biocenosis of the cave, with special emphasis on the relationship between human beings and animal species in this Upper Paleolithic sanctuary.

Our current results concern the cave bear, a species that became extinct 15,000 years ago. We evidenced in the Chauvet-Pont d’Arc Cave several mitochondrial haplotypes, that were widespread in the European cave bear population. Hence, the cave was not an isolated refuge, frequented by an animal population reproducing in autarky. The cave bear lineages are all contemporaneous with the oldest paintings, which may indicate the alternating occupancy of the cave, by cave bears during the cold season (hibernation) and by humans during other periods.

The remarkable preservation of bone remains prompted us to decipher the entirety of the cave bear mitochondrial genome. The sequencing is just about to be finished.

The characterization of the cave bear population will be pursued by analyzing remains from different archeological levels. Canidae samples will be studied to check for the possible presence of the dog.

                                       
©Ministère de la Culture et de la Communication, DRAC Rhône-Alpes, SRA


Key words
Theme 1: brain; transcriptome; secretome; SAGE; molecular markers.Theme 2: Chauvet Cave; ancient DNA; paleogenetics; cave bear; mitochondrial genome.


Publications
Bernay B, Gaillard MC, Guryca V, Emadali A, Kuhn L, Bertrand A, Detraz I, Carcenac C, Savasta M, Brouillet E, Garin J, Elalouf JM.  (2009). Discovering new bioactive neuropeptides in the striatum secretome using in vivo microdialysis and versatile proteomics. Mol Cell Proteomics. (Sous Presse).

Benchoua A, Trioulier Y, Diguet E, Malgorn C, Gaillard MC, Dufour N, Elalouf JM, Krajewski S, Hantraye P, Déglon N, Brouillet E.  (2008). Dopamine determines the vulnerability of striatal neurons to the N-terminal fragment of mutant huntingtin through the regulation of mitochondrial complex II. Hum Mol Genet.  17, 1446-56.

Bon C, Caudy N, de Dieuleveult M, Fosse P, Philippe M, Maksud F, Beraud-Colomb E, Bouzaid E, Kefi R, Laugier C, Rousseau B, Casane D, van der Plicht J, Elalouf JM.  (2008). Deciphering the complete mitochondrial genome and phylogeny of the extinct cave bear in the Paleolithic painted cave of Chauvet. Proc Natl Acad Sci U S A. 105, 17447-17452.

Brochier C, Gaillard MC, Diguet E, Caudy N, Dossat C, Segurens B, Wincker P, Roze E, Caboche J, Hantraye P, Brouillet E, Elalouf JM, de Chaldee M.  (2008). Quantitative gene expression profiling of mouse brain regions reveals differential transcripts conserved in man and affected in disease models. Physiol Genomics.  33, 170-9.

Guinobert I, Viltard M, Piquemal D, Elalouf JM, Marti J, Lelievre-Pegorier M.  (2006). Identification of differentially expressed genes between fetal and adult mouse kidney: candidate gene in kidney development. Nephron Physiol. 102, 81-91.

Cheval L, Morla L, Elalouf JM, Doucet A.  (2006). Kidney collecting duct acid-base "regulon". Physiol Genomics. 27, 271-281.

de Chaldée M, Brochier C, Van de Vel A, Caudy N, Luthi-Carter R, Gaillard MC, Elalouf JM.  (2006). Capucin: a novel striatal marker down-regulated in rodent models of Huntington disease. Genomics. 87, 200-207.

Bourdet A, Ciaudo C, Zakin L, Elalouf JM, Rusniok C, Weissenbach J, Avner P.  (2006). A SAGE approach to identifying novel trans-acting factors involved in the X inactivation process. Cytogenet Genome Res. 113, 325-335.

Benchoua A, Trioulier Y, Zala D, Gaillard MC, Lefort N, Dufour N, Saudou F, Elalouf JM, Hirsch E, Hantraye P, Deglon N, Brouillet E.  (2006). Involvement of Mitochondrial Complex II Defects in Neuronal Death Produced by N-Terminus Fragment of Mutated Huntingtin. Mol Biol Cell. 17, 1652-1663.

Zala D, Benchoua A, Brouillet E, Perrin V, Gaillard MC, Zurn AD, Aebischer P, Deglon N.  (2005). Progressive and selective striatal degeneration in primary neuronal cultures using lentiviral vector coding for a mutant huntingtin fragment. Neurobiol Dis. 20, 785-798.
 
Mansour H, Cheval L, Elalouf JM, Aude JC, Alyanakian MA, Mougenot B, Doucet A, Deschenes G.  (2005). T-cell transcriptome analysis points up a thymic disorder in idiopathic nephrotic syndrome Kidney Int. 67, 2168-2177.

Assie G, Auzan C, Gasc JM, Baviera E, Balaton A, Elalouf JM, Jeunemaitre X, Plouin PF, Corvol P, Clauser E.  (2005). Steroidogenesis in Aldosterone-Producing Adenoma revisited by transcriptome analysis. J Clin Endocrinol Metab. 90, 6638-6649.

Artagaveytia N, Elalouf JM, de Rouffignac C, Boivin R, Cirio A.  (2005). Expression of urea transporter (UT-A) mRNA in papilla and pelvic epithelium of kidney in normal and low protein fed sheep. Comp Biochem Physiol B Biochem Mol Biol. 140, 279-285.

Cheval L, Duong Van Huyen JP, Bruneval P, Verbavatz JM, Elalouf JM, Doucet A.  (2004). Plasticity of mouse renal collecting duct in response to potassium depletion. Physiol Genomics. 19, 61-73.

de Chaldée M, Gaillard MC, Bizat N, Buhler JM, Manzoni O, Bockaert J, Hantraye P, Brouillet E, Elalouf JM.  (2003). Quantitative assessment of transcriptome differences between brain territories. Genome Res. 13, 1646-1653.

Chabardès-Garonne D, Méjean A, Aude  JC, Cheval L, Di Stefano A, Gaillard MC, Imbert-Teboul M, Wittner M, Balian C, Anthouard V, Robert C, Ségurens B, Wincker P, Weissenbach J, Doucet A, Elalouf JM.  (2003). A panoramic view of gene expression in the human kidney. Proc Natl Acad Sci U S A. 100, 13710-13715.

Piquemal D, Commes T, Manchon L, Lejeune M, Ferraz C, Pugnere D, Demaille J, Elalouf JM, Marti J.  (2002). Transcriptome analysis of monocytic leukemia cell differentiation. Genomics. 80, 361-371.

Elalouf JM, Aude JC, Billon E, Cheval L, Doucet A, Virlon B.  (2002).  Renal transcriptomes: segmental analysis of differential expression. Exp Nephrol.  10,  75-81.

Cheval L, Virlon B, Billon E, Aude JC, Elalouf JM, Doucet A.  (2002).  Large-scale analysis of gene expression: methods and application to the kidney. J Nephrol.  15,  S170-S183.

Robert-Nicoud M, Flahaut M, Elalouf JM, Nicod M, Salinas M, Bens M, Doucet A, Wincker P, Artiguenave F, Horisberger JD, Vandewalle A, Rossier BC, Firsov D.  (2001). Transcriptome of a mouse kidney cortical collecting duct cell line : effects of aldosterone and vasopressin Proc Natl Acad Sci U S A. 98, 2712-2716.

Zakin L, Reversade B, Virlon B, Rusniok C, Glaser P, Elalouf JM, Brulet P.  (2000). Gene expression profiles in normal and Otx2-/- early gastrulating mouse embryos Proc Natl Acad Sci U S A. 97, 14388-14393. 

Virlon B, Cheval L, Buhler JM, Billon E, Doucet A, Elalouf JM.  (1999). Serial microanalysis of renal transcriptomes Proc Natl Acad Sci U S A. 96, 15286-15291. 

Troispoux C, Guillou F, Elalouf JM, Firsov D, Iacovelli L, De Blasi A, Combarnous Y, Reiter E.  (1999). Involvement of G protein-coupled receptor kinases and arrestins in desensitization to follicle-stimulating hormone action Mol Endocrinol. 13, 1599-1614. 

Chabardès D, Imbert-Teboul M, Elalouf JM.  (1999). Functional properties of Ca2+-inhibitable type 5 and type 6 adenylyl cyclases and role of Ca2+ increase in the inhibition intracellular cAMP content - Topical review Cell Signal. 11, 651-663. 

Chabardès D, Elalouf JM, Aarab L.  (1999). Regulation of intracellular cAMP content in kidney tubules: role of adenylyl cyclases inhibitable by calcium Nephrologie. 20, 193-201. 


Main collaborations
Thème 1 : P. Hantraye (DSV/I2BM/MIRCen/CEA Orsay) & J. Garin (DSV/iRTSV/LEDyP/CEA Grenoble)

Thème 2 : B. Rousseau (DSV/iBiTec-S/SCBM/CEA Saclay)