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0027-8424103132006Mar28Proceedings of the National Academy of Sciences of the United States of AmericaProc Natl Acad Sci U S ANeurogenin1 is a determinant of zebrafish basal forebrain dopaminergic neurons and is regulated by the conserved zinc finger protein Tof/Fezl.514351485143-8The development of vertebrate basal forebrain dopaminergic (DA) neurons requires the conserved zinc finger protein Too Few (Tof/Fezl) in zebrafish. However, how Tof/Fezl regulates the commitment and differentiation of these DA neurons is not known. Proneural genes encoding basic helix-loop-helix transcription factors regulate the development of multiple neuronal lineages, but their involvement in vertebrate DA neuron determination is unclear. Here we show that neurogenin 1 (ngn1), a vertebrate proneural gene related to the Drosophila atonal, is expressed in and required for specification of DA progenitor cells, and when overexpressed leads to supernumerary DA neurons in the forebrain of zebrafish. Overexpression of ngn1 is also sufficient to induce tyrosine hydroxylase expression in addition to the pan-neuronal marker Hu in nonneural ectoderm. We further show that Tof/Fezl is required to establish basal forebrain ngn1-expressing DA progenitor domains. These findings identify Ngn1 as a determinant of brain DA neurons and provide insights into how Tof/Fezl regulates the development of these clinically important neuronal types.JeongJae-YeonJYDepartment of Biopharmaceutical Sciences, Program in Human Genetics, University of California, San Francisco, CA 94143, USA.EinhornZevZMercurioSaraSLeeSusieSLauBillyBMioneMarinaMWilsonStephen WSWGuoSuSengWT_Wellcome TrustUnited KingdomGFP03011TI_TelethonItalyJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't20060320
United StatesProc Natl Acad Sci U S A75058760027-84240Basic Helix-Loop-Helix Proteins0Carrier ProteinsVTD58H1Z2XDopamine0Nerve Tissue ProteinsEC 1.14.16.2Tyrosine 3-Monooxygenase0Zebrafish Proteins0fezf2 protein, zebrafish0neurog1 protein, zebrafishIMAnimalsBasic Helix-Loop-Helix ProteinsgeneticsmetabolismCarrier ProteinschemistrygeneticsmetabolismCell ShapeConserved SequenceDopaminebiosynthesismetabolismEctodermcytologymetabolismGene Expression Regulation, DevelopmentalMutationgeneticsNerve Tissue ProteinsgeneticsmetabolismNeuronscytologymetabolismProsencephaloncytologyembryologymetabolismStem CellsmetabolismTyrosine 3-MonooxygenasemetabolismZebrafishembryologygeneticsmetabolismZebrafish ProteinschemistrygeneticsmetabolismZinc FingersConflict of interest statement: No conflicts declared.2006322902006511902006322902006928ppublish16549779PMC145880810.1073/pnas.06003371030600337103Goridis C., Rohrer H. Nat. Rev. Neurosci. 2002;3:531–541.12094209Zetterström R. H., Solomin L., Jansson L., Hoffer B. J., Olson L., Perlmann T. Science. 1997;276:248–250.9092472Smidt M. P., Asbreuk C. H. J., Cox J. J., Chen H., Johnson R. L., Burbach J. P. H. Nat. Neurosci. 2000;3:337–341.10725922Guo S., Yamaguchi Y., Schilbach S., Wada T., Goddard A., Lee J., French D., Handa H., Rosenthal A. Nature. 2000;408:366–369.11099044Levkowitz G., Zeller J., Sirotkin H. I., French D., Schilbach S., Hashimoto H., Hibi M., Talbot W. S., Rosenthal A. Nat. Neurosci. 2003;6:28–33.12469125Vitalis T., Cases O., Engelkamp D., Verney C., Price D. J. J. Neurosci. 2000;20:6501–6516.PMC677295910964956Andrews G. L., Yun K., Rubenstein J., Mastick G. S. Mol. Cell. Neurosci. 2003;23:107–120.12799141Guo S., Wilson S. W., Cooke S., Chitnis A. B., Driever W., Rosenthal A. Dev. Biol. 1999;208:473–487.10191060Holzschuh J., Ryu S., Aberger F., Driever W. Mech. Dev. 2001;101:237–243.11231083Rink E., Wullimann M. F. Brain Res. 2001;889:316–330.11166725Kapsimali M., Bourrat F., Vernier P. J. Comp. Neurol. 2001;431:276–292.11170005Jan Y. N., Jan L. Y. Cell. 1993;75:827–830.8252617Chitnis A. B. Curr. Opin. Neurobiol. 1999;9:18–25.10072374Bertrand N., Castro D. S., Guillemot F. Nat. Rev. Neurosci. 2002;3:517–530.12094208Jarman A. P., Grau Y., Jan L. Y., Jan Y. N. Cell. 1993;73:1307–1321.8324823Ma Q., Kintner C., Anderson D. J. Cell. 1996;87:43–52.8858147Sommer L., Ma Q., Anderson D. J. Mol. Cell Neurosci. 1996;8:221–241.9000438Ma Q., Fode C., Guillemot F., Anderson D. J. Genes Dev. 1999;13:1717–1728.PMC31684410398684Ma Q., Chen Z., Barrantes I., Pompa J., Anderson D. J. Neuron. 1998;20:469–482.9539122Fode C., Gradwohl G., Morin X., Dierich A., LeMeur M., Goridis C., Guillemot F. Neuron. 1998;20:483–494.9539123Blader P., Fischer N., Gradwohl G., Guillemot F., Strahle U. Development (Cambridge, U.K.) 1997;124:4557–4569.9409673Andermann P., Ungos J., Raible D. W. Dev. Biol. 2002;251:45–58.12413897Cornell R. A., Eisen J. S. Development (Cambridge, U.K.) 2002;129:2639–2648.12015292Cau E., Wilson S. W. Development (Cambridge, U.K.) 2003;130:2455–2466.12702659Blader P., Plessy C., Strahle U. Mech. Dev. 2003;120:211–218.12559493Halloran M. C., Sato-Maeda M., Warren J. T., Su F., Lele Z., Krone P. H., Kuwada J. Y., Shoji W. Development (Cambridge, U.K.) 2000;127:1953–1960.10751183Amsterdam A., Nissen R. M., Sun Z., Swindell E. C., Farrington S., Hopkins N. Proc. Natl. Acad. Sci. USA. 2004;101:12792–12797.PMC51647415256591Sakurada K., Ohshima-Sakurada M., Palmer T. D., Gage F. H. Development (Cambridge, U.K.) 1999;126:4017–4026.10457011Andersson E., Jensen J. B., Parmar M., Guillemot F., Bjorklund A. Development (Cambridge, U.K.) 2006;133:507–516.16396906Lau B., Bretaud S., Huang Y., Lin E., Guo S. Genes Brain Behav. 2005 in press.17010096Guo S., Driever W., Rosenthal A. Handbook of Molecular-Genetic Techniques for Brain and Behavior Research. Amsterdam: Elsevier; 1999. pp. 166–176.Kimmel C. B., Ballard W. W., Kimmel S. R., Ullmann B., Schilling T. F. Dev. Dyn. 1995;203:253–310.8589427Concha M. L., Russell C., Regan J. C., Tawk M., Sidi S., Gilmour D. T., Kapsimali M., Sumoy L., Goldstone K., Amaya E., et al. Neuron. 2003;39:423–438.12895418Guo S., Brush J., Teraoka H., Goddard A., Wilson S. W., Mullins M. C., Rosenthal A. Neuron. 1999;24:555–566.10595509Andersson E., Tryggvason U., Deng Q., Friling S., Alekseenko Z., Robert B., Perlmann T., Ericson J. Cell. 2006;124:393–405.16439212