The Team
  • Researchers

    Norbert GHYSELINCK

    Manuel MARK

    Marius TELETIN

    Nadège VERNET

  • Engineers & Technicians

    Betty FERET

    Muriel KLOPFENSTEIN

  • Master

    Irina SHAKHOVA

Functional genomics and cancer

Retinoic acid signaling pathways driving stem spermatogonia ontogenesis and differentiation

Retinoic acid (RA), the biologically active metabolite of vitamin A, exerts a wide range of cellular effects by regulating proliferation, differentiation and apoptosis. At the cellular level, the action of RA is controlled through the modulated expression of cellular enzymes producing or degrading RA, retinaldehyde dehydrogenases (RALDH) or cytochrome P450 hydroxylases (CYP26), respectively. Then, acting in an hormone-like manner, RA binds to nuclear receptors (RAR) that function as transcriptional regulators through controlling, usually in the form of heterodimers with rexinoid receptors (RXR), the expression of RA target genes. Among the various tissues whose physiology depends upon vitamin A action, the seminiferous epithelium of the testis represents the most remarkable paradigm to investigate the pleiotropic effects of RA in vivo, as it integrates the problematic of stem cell renewal, cell proliferation, switching from mitotic to meiotic cell division, programmed cell death and paracrine signaling. Using a combination of innovative genetic, pharmacological and molecular approaches in the mouse, we are studying the cellular and molecular mechanisms that underlie the capabilities of RA to promote spermatogonia differentiation and beyond the differentiation of normal stem cells in vivo.

  • Current projects

  • Collaborations

  • Prizes/Awards

  • News

  • Publications

    • High-throughput discovery of novel developmental phenotypes.

      Dickinson ME(1), Flenniken AM(2,)(3), Ji X(4), Teboul L(5), Wong MD(2,)(6), White JK(7), Meehan TF(8), Weninger WJ(9), Westerberg H(5), Adissu H(2,)(10), Baker CN(11), Bower L(12), Brown JM(5), Caddle LB(11), Chiani F(13), Clary D(12), Cleak J(5), Daly MJ(14,)(15), Denegre JM(11), Doe B(7), Dolan ME(11), Edie SM(11), Fuchs H(16), Gailus-Durner V(16), Galli A(7), Gambadoro A(13), Gallegos J(17), Guo S(18), Horner NR(5), Hsu CW(1), Johnson SJ(5), Kalaga S(1), Keith LC(1), Lanoue L(12), Lawson TN(5), Lek M(14,)(15), Mark M(19), Marschall S(16), Mason J(8), McElwee ML(1), Newbigging S(2,)(10), Nutter LM(2,)(10), Peterson KA(11), Ramirez-Solis R(7), Rowland DJ(12), Ryder E(7), Samocha KE(14,)(15), Seavitt JR(17), Selloum M(19), Szoke-Kovacs Z(5), Tamura M(20), Trainor AG(12), Tudose I(8), Wakana S(20), Warren J(8), Wendling O(19), West DB(21), Wong L(1), Yoshiki A(20); International Mouse Phenotyping Consortium; Jackson Laboratory; Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS); Charles River Laboratories; MRC Harwell; Toronto Centre for Phenogenomics; Wellcome Trust Sanger Institute; RIKEN BioResource Center, MacArthur DG(14,)(15), Tocchini-Valentini GP(13), Gao X(18), Flicek P(8), Bradley A(7), Skarnes WC(7), Justice MJ(10,)(17), Parkinson HE(8), Moore M(22), Wells S(5), Braun RE(11), Svenson KL(11), de Angelis MH(16,)(23,)(24), Herault Y(19), Mohun T(25), Mallon AM(5), Henkelman RM(2,)(6), Brown SD(5), Adams DJ(7), Lloyd KC(12), McKerlie C(2,)(10), Beaudet AL(17), Bu?an M(26), Murray SA(11).

      Nature Sept. 14, 2016 .

    • High-throughput discovery of novel developmental phenotypes.

      Dickinson ME(1), Flenniken AM(2,)(3), Ji X(4), Teboul L(5), Wong MD(2,)(6), White JK(7), Meehan TF(8), Weninger WJ(9), Westerberg H(5), Adissu H(2,)(10), Baker CN(11), Bower L(12), Brown JM(5), Caddle LB(11), Chiani F(13), Clary D(12), Cleak J(5), Daly MJ(14,)(15), Denegre JM(11), Doe B(7), Dolan ME(11), Edie SM(11), Fuchs H(16), Gailus-Durner V(16), Galli A(7), Gambadoro A(13), Gallegos J(17), Guo S(18), Horner NR(5), Hsu CW(1), Johnson SJ(5), Kalaga S(1), Keith LC(1), Lanoue L(12), Lawson TN(5), Lek M(14,)(15), Mark M(19), Marschall S(16), Mason J(8), McElwee ML(1), Newbigging S(2,)(10), Nutter LM(2,)(10), Peterson KA(11), Ramirez-Solis R(7), Rowland DJ(12), Ryder E(7), Samocha KE(14,)(15), Seavitt JR(17), Selloum M(19), Szoke-Kovacs Z(5), Tamura M(20), Trainor AG(12), Tudose I(8), Wakana S(20), Warren J(8), Wendling O(19), West DB(21), Wong L(1), Yoshiki A(20); International Mouse Phenotyping Consortium; Jackson Laboratory; Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS); Charles River Laboratories; MRC Harwell; Toronto Centre for Phenogenomics; Wellcome Trust Sanger Institute; RIKEN BioResource Center, MacArthur DG(14,)(15), Tocchini-Valentini GP(13), Gao X(18), Flicek P(8), Bradley A(7), Skarnes WC(7), Justice MJ(10,)(17), Parkinson HE(8), Moore M(22), Wells S(5), Braun RE(11), Svenson KL(11), de Angelis MH(16,)(23,)(24), Herault Y(19), Mohun T(25), Mallon AM(5), Henkelman RM(2,)(6), Brown SD(5), Adams DJ(7), Lloyd KC(12), McKerlie C(2,)(10), Beaudet AL(17), Bu?an M(26), Murray SA(11).

      Nature Sept. 14, 2016 .

    • High-throughput discovery of novel developmental phenotypes.

      Dickinson ME(1), Flenniken AM(2,)(3), Ji X(4), Teboul L(5), Wong MD(2,)(6), White JK(7), Meehan TF(8), Weninger WJ(9), Westerberg H(5), Adissu H(2,)(10), Baker CN(11), Bower L(12), Brown JM(5), Caddle LB(11), Chiani F(13), Clary D(12), Cleak J(5), Daly MJ(14,)(15), Denegre JM(11), Doe B(7), Dolan ME(11), Edie SM(11), Fuchs H(16), Gailus-Durner V(16), Galli A(7), Gambadoro A(13), Gallegos J(17), Guo S(18), Horner NR(5), Hsu CW(1), Johnson SJ(5), Kalaga S(1), Keith LC(1), Lanoue L(12), Lawson TN(5), Lek M(14,)(15), Mark M(19), Marschall S(16), Mason J(8), McElwee ML(1), Newbigging S(2,)(10), Nutter LM(2,)(10), Peterson KA(11), Ramirez-Solis R(7), Rowland DJ(12), Ryder E(7), Samocha KE(14,)(15), Seavitt JR(17), Selloum M(19), Szoke-Kovacs Z(5), Tamura M(20), Trainor AG(12), Tudose I(8), Wakana S(20), Warren J(8), Wendling O(19), West DB(21), Wong L(1), Yoshiki A(20); International Mouse Phenotyping Consortium; Jackson Laboratory; Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS); Charles River Laboratories; MRC Harwell; Toronto Centre for Phenogenomics; Wellcome Trust Sanger Institute; RIKEN BioResource Center, MacArthur DG(14,)(15), Tocchini-Valentini GP(13), Gao X(18), Flicek P(8), Bradley A(7), Skarnes WC(7), Justice MJ(10,)(17), Parkinson HE(8), Moore M(22), Wells S(5), Braun RE(11), Svenson KL(11), de Angelis MH(16,)(23,)(24), Herault Y(19), Mohun T(25), Mallon AM(5), Henkelman RM(2,)(6), Brown SD(5), Adams DJ(7), Lloyd KC(12), McKerlie C(2,)(10), Beaudet AL(17), Bu?an M(26), Murray SA(11).

      Nature Sept. 14, 2016 .

    • Role of the BAHD1 Chromatin-Repressive Complex in Placental Development and Regulation of Steroid Metabolism.

      Lakisic G(1), Lebreton A(2,)(3,)(4), Pourpre R(1), Wendling O(5), Libertini E(6), Radford EJ(7,)(8), Le Guillou M(9), Champy MF(5), Wattenhofer-Donze M(5), Soubigou G(6), Ait-Si-Ali S(10), Feunteun J(9), Sorg T(5), Coppee JY(6), Ferguson-Smith AC(7), Cossart P(2,)(3,)(4), Bierne H(1).

      PLoS Genet March 3, 2016 ; 12:e1005898 .

    • Mouse Y-Encoded Transcription Factor Zfy2 Is Essential for Sperm Head Remodelling and Sperm Tail Development.

      Vernet N(1,)(2), Mahadevaiah SK(1,)(3), Decarpentrie F(1,)(3), Longepied G(4,)(5), de Rooij DG(6,)(7), Burgoyne PS(1), Mitchell MJ(4,)(5).

      PLoS One Jan. 14, 2016 ; 11:e0145398 .

    • CO-34: Retinoic acid receptor signaling contributes to adrenal morphology and functional zonation.

      Boulkroun S(1), Rickard A(1), Golib Dzib J(2), Samson-Couterie B(1), Rocha A(1), Gomez-Sanchez C(3), Rainey W(4), Amar L(5), Fernandes-Rosa F(6), Ghyselinck N(7), Benecke A(2), Lalli E(8), Zennaro M(6).

      Ann Cardiol Angeiol (Paris) Dec 2015 2015 ; 64:S16 .

    • Loss of Projections, Functional Compensation, and Residual Deficits in the Mammalian Vestibulospinal System of Hoxb1-Deficient Mice.

      Di Bonito M(1), Boulland JL(2), Krezel W(3), Setti E(1), Studer M(1), Glover JC(2).

      eNeuro Dec. 26, 2015 ; 2:e0096-15 .

    • Retinoic Acid Receptors Control Spermatogonia Cell-Fate and Induce Expression of the SALL4A Transcription Factor.

      Gely-Pernot A(1), Raverdeau M(1), Teletin M(2), Vernet N(1), Féret B(1), Klopfenstein M(1), Dennefeld C(1), Davidson I(1), Benoit G(3), Mark M(2), Ghyselinck NB(1).

      PLoS Genet Oct. 1, 2015 ; 11:e1005501 .

    • Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics.

      Hrabe de Angelis M, Nicholson G, Selloum M, White JK, Morgan H, Ramirez-Solis R, Sorg T, Wells S, Fuchs H, Fray M, Adams DJ, Adams NC, Adler T, Aguilar-Pimentel A, Ali-Hadji D, Amann G, AndrE P, Atkins S, Auburtin A, Ayadi A, Becker J, Becker L, Bedu E, Bekeredjian R, Birling MC, Blake A, Bottomley J, Bowl MR, Brault V, Busch DH, Bussell JN, Calzada-Wack J, Cater H, Champy MF, Charles P, Chevalier C, Chiani F, Codner GF, Combe R, Cox R, Dalloneau E, Dierich A, Di Fenza A, Doe B, Duchon A, Eickelberg O, Esapa CT, Fertak LE, Feigel T, Emelyanova I, Estabel J, Favor J, Flenniken A, Gambadoro A, Garrett L, Gates H, Gerdin AK, Gkoutos G, Greenaway S, Glasl L, Goetz P, Da Cruz IG, Gotz A, Graw J, Guimond A, Hans W, Hicks G, Holter SM, Hofler H, Hancock JM, Hoehndorf R, Hough T, Houghton R, Hurt A, Ivandic B, Jacobs H, Jacquot S, Jones N, Karp NA, Katus HA, Kitchen S, Klein-Rodewald T, Klingenspor M, Klopstock T, Lalanne V, Leblanc S, Lengger C, le Marchand E, Ludwig T, Lux A, McKerlie C, Maier H, Mandel JL, Marschall S, Mark M, Melvin DG, Meziane H, Micklich K, Mittelhauser C, Monassier L, Moulaert D, Muller S, Naton B, Neff F, Nolan PM, Nutter LM, Ollert M, Pavlovic G, Pellegata NS, Peter E, Petit-Demouliere B, Pickard A, Podrini C, Potter P, Pouilly L, Puk O, Richardson D, Rousseau S, Quintanilla-Fend L, Quwailid MM, Racz I, Rathkolb B, Riet F, Rossant J, Roux M, Rozman J, Ryder E, Salisbury J, Santos L, Schable KH, Schiller E, Schrewe A, Schulz H, Steinkamp R, Simon M, Stewart M, Stoger C, Stoger T, Sun M, Sunter D, Teboul L, Tilly I, Tocchini-Valentini GP, Tost M, Treise I, Vasseur L, Velot E, Vogt-Weisenhorn D, Wagner C, Walling A, Wattenhofer-Donze M, Weber B, Wendling O, Westerberg H, Willershauser M, Wolf E, Wolter A, Wood J, Wurst W, Yildirim AO, Zeh R, Zimmer A, Zimprich A; EUMODIC Consortium, Holmes C, Steel KP, Herault Y, Gailus-Durner V, Mallon AM, Brown SD.

      Nat Genet Sep 2015 ; 47:969-78 .

    • Exome sequencing reveals a nonsense mutation in TEX15 causing spermatogenic failure in a Turkish family.

      Okutman O(1), Muller J(2), Baert Y(3), Serdarogullari M(4), Gultomruk M(4), Piton A(2), Rombaut C(3), Benkhalifa M(5), Teletin M(1), Skory V(6), Bakircioglu E(7), Goossens E(3), Bahceci M(4), Viville S(8).

      Hum Mol Genet Oct. 1, 2015 ; 24:5581-8 .

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Imprimer Envoyer

Université de Strasbourg
INSERM
CNRS

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