Zebrafish: An integrative system for neurogenomics and neurosciences

Rapid technological advances over the past decade have moved us closer to a high throughput molecular approach to neurobiology, where we see the merging of neurogenetics, genomics, physiology, imaging and pharmacology. This is the case more in zebrafish than in any other model organism commonly used. Recent improvements in the generation of transgenic zebrafish now allow genetic manipulation and live imaging of neuronal development and function in early embryonic, larval, and adult animals. The sequenced zebrafish genome and comparative genomics give unprecedented insights into genome evolution and its relation to genome structure and function. There is now information on embryonic and larval expression of over 12,000 genes and just under 1000 mutant phenotypes. We review the remarkable similarity of the zebrafish genetic blueprint for the nervous system to that of mammals and assess recent technological advances that make the zebrafish a model of choice for elucidating the development and function of neuronal circuitry, transgene-based neuroanatomy, and small molecule neuropharmacology.

[1]  B. Oostra,et al.  A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. , 2003, Human molecular genetics.

[2]  H. Bellen,et al.  Ten Years of Enhancer Detection: Lessons from the Fly , 1999, Plant Cell.

[3]  Eva A Naumann,et al.  Monitoring Neural Activity with Bioluminescence during Natural Behavior , 2010, Nature Neuroscience.

[4]  N. Heintz Gene Expression Nervous System Atlas (GENSAT) , 2004, Nature Neuroscience.

[5]  Hironobu Ito,et al.  Non-laminar cerebral cortex in teleost fishes? , 2009, Biology Letters.

[6]  Philippe Vernier,et al.  The adult central nervous cholinergic system of a neurogenetic model animal, the zebrafish Danio rerio , 2004, Brain Research.

[7]  Boris Lenhard,et al.  Synorth: exploring the evolution of synteny and long-range regulatory interactions in vertebrate genomes , 2009, Genome Biology.

[8]  Boris Lenhard,et al.  Retroviral enhancer detection insertions in zebrafish combined with comparative genomics reveal genomic regulatory blocks - a fundamental feature of vertebrate genomes , 2007, Genome Biology.

[9]  H Okamoto,et al.  Visualization of Cranial Motor Neurons in Live Transgenic Zebrafish Expressing Green Fluorescent Protein Under the Control of the Islet-1 Promoter/Enhancer , 2000, The Journal of Neuroscience.

[10]  Jonathan E. Foley,et al.  Rapid Mutation of Endogenous Zebrafish Genes Using Zinc Finger Nucleases Made by Oligomerized Pool ENgineering (OPEN) , 2009, PloS one.

[11]  H. Kawauchi Functions of melanin-concentrating hormone in fish. , 2006, Journal of experimental zoology. Part A, Comparative experimental biology.

[12]  M. Wullimann,et al.  An Evolutionary Interpretation of Teleostean Forebrain Anatomy , 2009, Brain, Behavior and Evolution.

[13]  K. Howe,et al.  Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates. , 2007, Genome research.

[14]  Laure Bally-Cuif,et al.  The zebrafish as a model system for assessing the reinforcing properties of drugs of abuse. , 2006, Methods.

[15]  D A Kane,et al.  Genes controlling and mediating locomotion behavior of the zebrafish embryo and larva. , 1996, Development.

[16]  D A Kane,et al.  Mutations in zebrafish genes affecting the formation of the boundary between midbrain and hindbrain. , 1996, Development.

[17]  S. Ekker,et al.  Effective targeted gene ‘knockdown’ in zebrafish , 2000, Nature Genetics.

[18]  B. Lenhard,et al.  New technologies, new findings, and new concepts in the study of vertebrate cis‐regulatory sequences , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[19]  Michael T. McManus,et al.  Dicer1 and miR-219 Are Required for Normal Oligodendrocyte Differentiation and Myelination , 2010, Neuron.

[20]  Christian Laggner,et al.  Rapid behavior—based identification of neuroactive small molecules in the zebrafish , 2009, Nature chemical biology.

[21]  I. Seiliez,et al.  Spatial and temporal expression of the zebrafish genome by large-scale in situ hybridization screening. , 2004, Methods in cell biology.

[22]  Ethan K. Scott,et al.  Optogenetic dissection of a behavioral module in the vertebrate spinal cord , 2009, Nature.

[23]  E. Mignot,et al.  Regulation of Hypocretin (Orexin) Expression in Embryonic Zebrafish* , 2006, Journal of Biological Chemistry.

[24]  Enhancer detection in the zebrafish using pseudotyped murine retroviruses. , 2006, Methods.

[25]  Q. Lu,et al.  MicroRNA-Mediated Control of Oligodendrocyte Differentiation , 2010, Neuron.

[26]  T. Wolfsberg,et al.  Identification of Neural Crest and Glial Enhancers at the Mouse Sox10 Locus through Transgenesis in Zebrafish , 2008, PLoS genetics.

[27]  H. Baier,et al.  Genetic dissection of the retinotectal projection. , 1996, Development.

[28]  R. Steiner,et al.  Kisspeptin signaling in the brain. , 2009, Endocrine reviews.

[29]  M. Ekker,et al.  Expression from a Dlx gene enhancer marks adult mouse cortical GABAergic neurons. , 2002, Cerebral cortex.

[30]  A. Amsterdam,et al.  A large-scale insertional mutagenesis screen in zebrafish. , 1999, Genes & development.

[31]  Bo Zhang,et al.  Efficient genome-wide mutagenesis of zebrafish genes by retroviral insertions , 2007, Proceedings of the National Academy of Sciences.

[32]  Alexander Borst,et al.  In Vivo Performance of Genetically Encoded Indicators of Neural Activity in Flies , 2005, The Journal of Neuroscience.

[33]  Nancy Hopkins,et al.  Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development , 2002, Nature Genetics.

[34]  Luca Muzio,et al.  Foxg1 Confines Cajal-Retzius Neuronogenesis and Hippocampal Morphogenesis to the Dorsomedial Pallium , 2005, The Journal of Neuroscience.

[35]  Boris Lenhard,et al.  Arrays of ultraconserved non-coding regions span the loci of key developmental genes in vertebrate genomes , 2004, BMC Genomics.

[36]  Su Guo,et al.  Use of zebrafish as a model to understand mechanisms of addiction and complex neurobehavioral phenotypes , 2010, Neurobiology of Disease.

[37]  Y. Gothilf,et al.  The zebrafish as a model system for forebrain GnRH neuronal development. , 2009, General and comparative endocrinology.

[38]  Emmanuel Mignot,et al.  Characterization of two melanin‐concentrating hormone genes in zebrafish reveals evolutionary and physiological links with the mammalian MCH system , 2009, The Journal of comparative neurology.

[39]  Herwig Baier,et al.  Optical control of zebrafish behavior with halorhodopsin , 2009, Proceedings of the National Academy of Sciences.

[40]  J. Vaughan,et al.  Characterization of melanin-concentrating hormone from rat hypothalamus. , 1989, Endocrinology.

[41]  Jan Kaslin,et al.  The Orexin/Hypocretin System in Zebrafish Is Connected to the Aminergic and Cholinergic Systems , 2004, The Journal of Neuroscience.

[42]  Philipp J. Keller,et al.  Reconstruction of Zebrafish Early Embryonic Development by Scanned Light Sheet Microscopy , 2008, Science.

[43]  M. Tena-Sempere,et al.  Evidence for two distinct KiSS genes in non-placental vertebrates that encode kisspeptins with different gonadotropin-releasing activities in fish and mammals , 2009, Molecular and Cellular Endocrinology.

[44]  Jonathan E. Foley,et al.  Targeted mutagenesis in zebrafish using customized zinc-finger nucleases , 2009, Nature Protocols.

[45]  A. Schier,et al.  A genetic screen for mutations affecting embryogenesis in zebrafish. , 1996, Development.

[46]  S. Neuhauss,et al.  Genetic identification of AChE as a positive modulator of addiction to the psychostimulant D-amphetamine in zebrafish. , 2006, Journal of neurobiology.

[47]  Markus Reischl,et al.  Automated high-throughput mapping of promoter-enhancer interactions in zebrafish embryos , 2009, Nature Methods.

[48]  G. Hannon,et al.  A MicroRNA Feedback Circuit in Midbrain Dopamine Neurons , 2007, Science.

[49]  John H. Postlethwait,et al.  Development and Stem Cells Research Article , 2022 .

[50]  L. Zon,et al.  Transparent adult zebrafish as a tool for in vivo transplantation analysis. , 2008, Cell stem cell.

[51]  K. Kawakami,et al.  Transposon-mediated BAC transgenesis in zebrafish and mice , 2009, BMC Genomics.

[52]  Herwig Baier,et al.  Targeting neural circuitry in zebrafish using GAL4 enhancer trapping , 2007, Nature Methods.

[53]  B. Thisse,et al.  Functions and regulations of fibroblast growth factor signaling during embryonic development. , 2005, Developmental biology.

[54]  N. Staudt,et al.  The Prethalamus Is Established during Gastrulation and Influences Diencephalic Regionalization , 2007, PLoS biology.

[55]  D. Price,et al.  The transcription factor Foxg1 regulates the competence of telencephalic cells to adopt subpallial fates in mice , 2010, Development.

[56]  N. Illing,et al.  Development of GnRH cells: Setting the stage for puberty , 2006, Molecular and Cellular Endocrinology.

[57]  H. Baier,et al.  Zebrafish mutations affecting retinotectal axon pathfinding. , 1996, Development.

[58]  K. Kawakami,et al.  Cis-regulation and chromosomal rearrangement of the fgf8 locus after the teleost/tetrapod split. , 2009, Developmental biology.

[59]  B. Thisse,et al.  High-resolution in situ hybridization to whole-mount zebrafish embryos , 2007, Nature Protocols.

[60]  P. Greengard,et al.  Cerebellar neurodegeneration in the absence of microRNAs , 2007, The Journal of experimental medicine.

[61]  N. Papalopulu,et al.  Integration of telencephalic Wnt and hedgehog signaling center activities by Foxg1. , 2009, Developmental cell.

[62]  Jun Li,et al.  Early Development of Functional Spatial Maps in the Zebrafish Olfactory Bulb , 2005, The Journal of Neuroscience.

[63]  David R Soll,et al.  Tyramine and octopamine have opposite effects on the locomotion of Drosophila larvae. , 2004, Journal of neurobiology.

[64]  Y. Hayashizaki,et al.  Transcriptional features of genomic regulatory blocks , 2009, Genome Biology.

[65]  D. Raible,et al.  Identification of Genetic and Chemical Modulators of Zebrafish Mechanosensory Hair Cell Death , 2008, PLoS genetics.

[66]  Carsten Marr,et al.  Zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine , 2009, Genome Biology.

[67]  M. Wullimann,et al.  Optimized Gal4 genetics for permanent gene expression mapping in zebrafish , 2009, Proceedings of the National Academy of Sciences.

[68]  Alexander F. Schier,et al.  Hypocretin/Orexin Overexpression Induces An Insomnia-Like Phenotype in Zebrafish , 2006, The Journal of Neuroscience.

[69]  Hiromi Hirata,et al.  touché Is Required for Touch-Evoked Generator Potentials within Vertebrate Sensory Neurons , 2010, The Journal of Neuroscience.

[70]  Ethan K. Scott,et al.  The cellular architecture of the larval zebrafish tectum , as revealed by Gal 4 enhancer trap lines , 2022 .

[71]  J. Mattick Deconstructing the Dogma , 2009, Annals of the New York Academy of Sciences.

[72]  B. Lenhard,et al.  Regulatory divergence of the duplicated chromosomal loci sox11a/b by subpartitioning and sequence evolution of enhancers in zebrafish , 2010, Molecular Genetics and Genomics.

[73]  Paulo P. Amaral,et al.  Noncoding RNA in development , 2008, Mammalian Genome.

[74]  H. Horvitz,et al.  MicroRNA Expression in Zebrafish Embryonic Development , 2005, Science.

[75]  Emmanuel Mignot,et al.  Characterization of Sleep in Zebrafish and Insomnia in Hypocretin Receptor Mutants , 2007, PLoS biology.

[76]  G. Fishell,et al.  Functional genomics of early cortex patterning , 2006, Genome Biology.

[77]  A. Amsterdam,et al.  Insertional mutagenesis in zebrafish identifies two novel genes, pescadillo and dead eye, essential for embryonic development. , 1996, Genes & development.

[78]  V. Laudet,et al.  Unexpected Novel Relational Links Uncovered by Extensive Developmental Profiling of Nuclear Receptor Expression , 2007, PLoS genetics.

[79]  K. Kawakami,et al.  Transient and stable transgenesis using tol2 transposon vectors. , 2009, Methods in molecular biology.

[80]  Karel Svoboda,et al.  Monitoring Neural Activity and [Ca2+] with Genetically Encoded Ca2+ Indicators , 2004, The Journal of Neuroscience.

[81]  V. Korzh,et al.  Tol2 transposon‐mediated enhancer trap to identify developmentally regulated zebrafish genes in vivo , 2004, Developmental dynamics : an official publication of the American Association of Anatomists.

[82]  J. Postlethwait,et al.  Evolutionary developmental biology and genomics , 2007, Nature Reviews Genetics.

[83]  Wolfgang Driever,et al.  Repressor activity of Headless/Tcf3 is essential for vertebrate head formation , 2000, Nature.

[84]  T. Becker,et al.  Genomic regulatory blocks in vertebrates and implications in human disease. , 2009, Briefings in functional genomics & proteomics.

[85]  B. Lenhard,et al.  Web-based tools and approaches to study long-range gene regulation in Metazoa. , 2009, Briefings in functional genomics & proteomics.

[86]  O. Garaschuk,et al.  Optical monitoring of brain function in vivo: from neurons to networks , 2006, Pflügers Archiv.

[87]  Jiangang Gao,et al.  A review of current large‐scale mouse knockout efforts , 2010, Genesis.

[88]  H. Kawauchi,et al.  Characterization of melanin-concentrating hormone in chum salmon pituitaries , 1983, Nature.

[89]  Boris Lenhard,et al.  Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes , 2008, Genome Biology.

[90]  E. Mignot,et al.  The neurobiology of hypocretins (orexins), narcolepsy and related therapeutic interventions. , 2006, Trends in pharmacological sciences.

[91]  Robert Baker,et al.  Mosaic hoxb4a Neuronal Pleiotropism in Zebrafish Caudal Hindbrain , 2009, PloS one.

[92]  Ima Paydar,et al.  Genomic Organization of Zebrafish microRNAs , 2008, BMC Genomics.

[93]  K. Kawakami,et al.  Targeted gene expression by the Gal4‐UAS system in zebrafish , 2008, Development, Growth and Differentiation.

[94]  A. Amsterdam,et al.  Transgenes as screening tools to probe and manipulate the zebrafish genome , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[95]  C. Nüsslein-Volhard,et al.  Genes involved in forebrain development in the zebrafish, Danio rerio. , 1996, Development.

[96]  Markus Reischl,et al.  Zebrafish embryos as models for embryotoxic and teratological effects of chemicals. , 2009, Reproductive toxicology.

[97]  Aristides B. Arrenberg,et al.  Optogenetic Localization and Genetic Perturbation of Saccade-Generating Neurons in Zebrafish , 2010, The Journal of Neuroscience.

[98]  Stephen W. Wilson,et al.  Early steps in the development of the forebrain. , 2004, Developmental cell.

[99]  Herwig Baier,et al.  Zebrafish on the move: towards a behavior–genetic analysis of vertebrate vision , 2000, Current Opinion in Neurobiology.

[100]  J. Postlethwait,et al.  Expression of sox11 gene duplicates in zebrafish suggests the reciprocal loss of ancestral gene expression patterns in development , 2000, Developmental dynamics : an official publication of the American Association of Anatomists.

[101]  Stephen W. Wilson,et al.  MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system , 2007, Genome Biology.

[102]  Mark J. Thomas,et al.  Nicotine response genetics in the zebrafish , 2009, Proceedings of the National Academy of Sciences.

[103]  S. Ben-Dor,et al.  Molecular Identification and Functional Characterization of the Kisspeptin/Kisspeptin Receptor System in Lower Vertebrates1 , 2008, Biology of reproduction.

[104]  S. Haggarty,et al.  Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation , 2010, Science.

[105]  Anton J. Enright,et al.  Zebrafish MiR-430 Promotes Deadenylation and Clearance of Maternal mRNAs , 2006, Science.

[106]  A. Schier,et al.  Target Protectors Reveal Dampening and Balancing of Nodal Agonist and Antagonist by miR-430 , 2007, Science.

[107]  S. Sivasubbu,et al.  Enhancer trapping in zebrafish using the Sleeping Beauty transposon , 2004, BMC Genomics.

[108]  Hiroshi Kikuta,et al.  Transgenesis in zebrafish with the tol2 transposon system. , 2009, Methods in molecular biology.

[109]  Wolfgang Driever,et al.  Genetic dissection of dopaminergic and noradrenergic contributions to catecholaminergic tracts in early larval zebrafish , 2009, The Journal of comparative neurology.

[110]  Philippe Vernier,et al.  Two tyrosine hydroxylase genes in vertebrates New dopaminergic territories revealed in the zebrafish brain , 2010, Molecular and Cellular Neuroscience.

[111]  G. Rubin,et al.  Global analysis of patterns of gene expression during Drosophila embryogenesis , 2007, Genome Biology.

[112]  M. Kapsimali,et al.  Enhancer detection and developmental expression of zebrafish sprouty1, a member of the fgf8 synexpression group , 2008, Developmental dynamics : an official publication of the American Association of Anatomists.

[113]  Thomas Becker,et al.  Adult zebrafish as a model for successful central nervous system regeneration. , 2008, Restorative neurology and neuroscience.

[114]  A. Meyer,et al.  The evolutionary significance of ancient genome duplications , 2009, Nature Reviews Genetics.

[115]  C. Niell,et al.  Functional Imaging Reveals Rapid Development of Visual Response Properties in the Zebrafish Tectum , 2005, Neuron.

[116]  H. Burgess,et al.  The neurogenetic frontier--lessons from misbehaving zebrafish. , 2008, Briefings in functional genomics & proteomics.

[117]  B. Griffond,et al.  Cell and molecular cell biology of melanin-concentrating hormone. , 2002, International review of cytology.

[118]  A Wenzel,et al.  Concentration- and Time-dependent Effects of the Synthetic Estrogen, 17α-ethinylestradiol, on Reproductive Capabilities of the Zebrafish, Danio rerio , 2007, Journal of toxicology and environmental health. Part A.

[119]  A. Amsterdam,et al.  Insertional mutagenesis in zebrafish: genes for development, genes for disease. , 2006, Briefings in functional genomics & proteomics.

[120]  Nancy Hopkins,et al.  Identification of 315 genes essential for early zebrafish development. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[121]  Sebastian T. Bundschuh,et al.  Optogenetic Dissection of Neuronal Circuits in Zebrafish using Viral Gene Transfer and the Tet System , 2009, Front. Neural Circuits.

[122]  M. Noyes,et al.  Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases , 2008, Nature Biotechnology.

[123]  D A Kane,et al.  The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. , 1996, Development.

[124]  Akihiro Urasaki,et al.  Insertional mutagenesis by the Tol2 transposon-mediated enhancer trap approach generated mutations in two developmental genes: tcf7 and synembryn-like , 2007, Development.

[125]  C. Claudianos,et al.  Big ideas for small brains: what can psychiatry learn from worms, flies, bees and fish? , 2011, Molecular Psychiatry.

[126]  E. Kremmer,et al.  The serotonergic phenotype is acquired by converging genetic mechanisms within the zebrafish central nervous system , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[127]  T. Becker,et al.  Segregation of telencephalic and eye-field identities inside the zebrafish forebrain territory is controlled by Rx3 , 2006, Development.

[128]  S. Megason,et al.  In toto imaging of embryogenesis with confocal time-lapse microscopy. , 2009, Methods in molecular biology.

[129]  C. Stigloher,et al.  MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary , 2008, Nature Neuroscience.

[130]  Jelena Erceg,et al.  Enhancer detection in zebrafish permits the identification of neuronal subtypes that express Hox4 paralogs , 2008, Developmental dynamics : an official publication of the American Association of Anatomists.

[131]  Nancy Hopkins,et al.  Insertional mutagenesis and rapid cloning of essential genes in zebrafish , 1996, Nature.

[132]  Dirk Trauner,et al.  A light-gated, potassium-selective glutamate receptor for the optical inhibition of neuronal firing , 2010, Nature Neuroscience.

[133]  A. Giráldez,et al.  MicroRNAs as genetic sculptors: fishing for clues. , 2010, Seminars in cell & developmental biology.

[134]  Anton J. Enright,et al.  Materials and Methods Figs. S1 to S4 Tables S1 to S5 References and Notes Micrornas Regulate Brain Morphogenesis in Zebrafish , 2022 .

[135]  D. Price,et al.  Foxg1 is required for specification of ventral telencephalon and region-specific regulation of dorsal telencephalic precursor proliferation and apoptosis. , 2005, Developmental biology.

[136]  L. Bally-Cuif,et al.  MicroRNAs in brain development and physiology , 2009, Current Opinion in Neurobiology.

[137]  Gail Mandel,et al.  Distribution of prospective glutamatergic, glycinergic, and GABAergic neurons in embryonic and larval zebrafish , 2004, The Journal of comparative neurology.

[138]  Shiaoching Gong,et al.  Modified bacterial artificial chromosomes for zebrafish transgenesis. , 2006, Methods.

[139]  Y. Gothilf,et al.  Period2 Expression Pattern and its Role in the Development of the Pineal Circadian Clock in Zebrafish , 2006, Chronobiology international.

[140]  T. Becker,et al.  Expression of the eight AMPA receptor subunit genes in the developing central nervous system and sensory organs of zebrafish , 2008, Developmental dynamics : an official publication of the American Association of Anatomists.

[141]  Su Guo,et al.  Using zebrafish to assess the impact of drugs on neural development and function , 2009, Expert opinion on drug discovery.

[142]  B. Lenhard,et al.  Exonic remnants of whole-genome duplication reveal cis-regulatory function of coding exons , 2009, Nucleic acids research.

[143]  Stephen W. Wilson,et al.  A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon. , 2001, Genes & development.

[144]  M. Harden,et al.  A role for foxd3 and sox10 in the differentiation of gonadotropin-releasing hormone (GnRH) cells in the zebrafish Danio rerio , 2005, Development.

[145]  Yan Zeng,et al.  Regulation of the Mammalian Nervous System by MicroRNAs , 2009, Molecular Pharmacology.

[146]  H. Baier,et al.  Mutations disrupting the ordering and topographic mapping of axons in the retinotectal projection of the zebrafish, Danio rerio. , 1996, Development.

[147]  Emmanuel Mignot,et al.  Sleep–wake regulation and hypocretin–melatonin interaction in zebrafish , 2009, Proceedings of the National Academy of Sciences.

[148]  Dopaminergic neuronal cluster size is determined during early forebrain patterning , 2008, Development.

[149]  Herwig Baier,et al.  Genetic and optical targeting of neural circuits and behavior—zebrafish in the spotlight , 2009, Current Opinion in Neurobiology.

[150]  P. Currie,et al.  Animal models of human disease: zebrafish swim into view , 2007, Nature Reviews Genetics.

[151]  Stephen W. Wilson,et al.  Establishment of the Telencephalon during Gastrulation by Local Antagonism of Wnt Signaling , 2002, Neuron.

[152]  Howard Cabral,et al.  Anxiogenic effects of cocaine withdrawal in zebrafish , 2008, Physiology & Behavior.

[153]  A. King Researchers Find Their Nemo , 2009, Cell.

[154]  O. Kah,et al.  Neuroendocrinology of reproduction in teleost fish. , 2010, General and comparative endocrinology.

[155]  T. Hocking,et al.  Heritable Targeted Gene Disruption in Zebrafish Using Designed Zinc Finger Nucleases , 2008, Nature Biotechnology.

[156]  Gord Fishell,et al.  The genetics of early telencephalon patterning: some assembly required , 2008, Nature Reviews Neuroscience.

[157]  D. V. Vactor,et al.  NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript NIH Public Access Author Manuscript Nat Methods. Author manuscript; available in PMC 2011 September 30. , 2009 .

[158]  Emmanuel Mignot,et al.  The Sleep Disorder Canine Narcolepsy Is Caused by a Mutation in the Hypocretin (Orexin) Receptor 2 Gene , 1999, Cell.

[159]  Hazel Sive,et al.  Coherent but overlapping expression of microRNAs and their targets during vertebrate development. , 2009, Genes & development.

[160]  Hae-Chul Park,et al.  Neural cell fate analysis in zebrafish using olig2 BAC transgenics. , 2003, Methods in cell science : an official journal of the Society for In Vitro Biology.

[161]  K. Kawakami,et al.  A transposon-mediated gene trap approach identifies developmentally regulated genes in zebrafish. , 2004, Developmental cell.

[162]  Herwig Baier,et al.  Remote Control of Neuronal Activity with a Light-Gated Glutamate Receptor , 2007, Neuron.

[163]  T. Becker,et al.  Large-scale enhancer detection in the zebrafish genome , 2005, Development.

[164]  Gregory M. Cahill,et al.  Circadian regulation of melatonin production in cultured zebrafish pineal and retina , 1996, Brain Research.

[165]  J. Sutcliffe,et al.  The hypocretins and sleep , 2005, The FEBS journal.

[166]  Laure Bally-Cuif,et al.  Adult zebrafish as a model organism for behavioural genetics , 2010, BMC Neuroscience.

[167]  E. Maratos-Flier,et al.  Expanding the scales: The multiple roles of MCH in regulating energy balance and other biological functions. , 2006, Endocrine reviews.

[168]  Scott E. Fraser,et al.  Imaging in Systems Biology , 2007, Cell.

[169]  S. Fisher,et al.  Conservation of RET Regulatory Function from Human to Zebrafish Without Sequence Similarity , 2006, Science.

[170]  P. Kille,et al.  Evidence for the existence of a functional Kiss1/Kiss1 receptor pathway in fish , 2008, Peptides.

[171]  Luis Puelles,et al.  Forebrain gene expression domains and the evolving prosomeric model , 2003, Trends in Neurosciences.

[172]  Boris Lenhard,et al.  Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3 , 2009, Proceedings of the National Academy of Sciences.

[173]  K. Rohr,et al.  Phenylthiourea disrupts thyroid function in developing zebrafish , 2002, Development Genes and Evolution.

[174]  A. Visel,et al.  ChIP-Seq identification of weakly conserved heart enhancers , 2010, Nature Genetics.

[175]  F. Engert,et al.  Escape Behavior Elicited by Single, Channelrhodopsin-2-Evoked Spikes in Zebrafish Somatosensory Neurons , 2008, Current Biology.

[176]  Florian Engert,et al.  The neural basis of visual behaviors in the larval zebrafish , 2009, Current Opinion in Neurobiology.

[177]  M. Wullimann,et al.  Phylotypic expression of the bHLH genes Neurogenin2, Neurod, and Mash1 in the mouse embryonic forebrain , 2010, The Journal of comparative neurology.

[178]  Emmanuel Mignot,et al.  Genomic and functional conservation of sedative-hypnotic targets in the zebrafish , 2007, Pharmacogenetics and genomics.

[179]  Edwin Cuppen,et al.  Efficient target-selected mutagenesis in zebrafish. , 2003, Genome research.

[180]  S. Ogawa,et al.  Cloning and expression of kiss2 in the zebrafish and medaka. , 2009, Endocrinology.

[181]  G. Fishell,et al.  The Role of Foxg1 and Dorsal Midline Signaling in the Generation of Cajal-Retzius Subtypes , 2007, The Journal of Neuroscience.

[182]  Jan Kaslin,et al.  Comparative anatomy of the histaminergic and other aminergic systems in zebrafish (Danio rerio) , 2001, The Journal of comparative neurology.

[183]  Boris Lenhard,et al.  Systematic human/zebrafish comparative identification of cis-regulatory activity around vertebrate developmental transcription factor genes. , 2009, Developmental biology.