ZFIN ID: ZDB-PERS-981030-19
Norton, Will
Email: whjn1@le.ac.uk
URL: http://www2.le.ac.uk/departments/npb/people/dr-will-norton
Affiliation: Norton Lab
Address: Norton Lab Department of Neuroscience, Psychology and Behaviour University of Leicester University Rd Leicester LE1 7RH UK
Phone: 0044 116 252 5078
Fax: 0044 116 252 3330

My research focuses on genes, neural circuits and human diseases that are connected to aggression using zebrafish (Danio rerio) as a model organism.

One area of my research centres on measuring the aggression-boldness behavioural syndrome (a positive correlation between aggression, boldness and exploration levels) in groups of adult zebrafish that harbour mutations in single genes. A key aspect of this work focuses upon measuring and comparing multiple behavioural changes in a single animal, giving insights into the pleiotropic action of the genes that control behaviour. Through comparison of the behavioural phenotype of different mutant families, we aim to uncover the general brain areas and genetic pathways that are linked to aggression-boldness in the vertebrate brain.

A second aim of my research is to study the neurodevelopmental function of genes which are linked to Attention Deficit/Hyperactivity Disorder (ADHD) in human patients. ADHD is a common psychiatric disorder that causes inattention, hyperactivity and impulsivity. Although predominantly a childhood disease, ADHD can also be maintained into adulthood and lead to increases in aggression. However, despite the large number of genes that have been identified by genome-wide association studies of human ADHD patients, the changes in neural development that lead to symptoms of the disease are not well understood. In my work, I use larval zebrafish to uncover the function of some of these ADHD-related genes. We have already identified ADHD-linked alterations to larval zebrafish behaviour, including locomotor hyperactivity and motor impulsivity. By combining gene expression analyses with measurements of the behavioural impact of loss-of-gene function, we thus aim to better understand how alterations of genes that are identified in genome-wide association studies contribute to the symptoms of ADHD.

Antón-Galindo, E., Adel, M.R., García-González, J., Leggieri, A., López-Blanch, L., Irimia, M., Norton, W.H.J., Brennan, C.H., Fernàndez-Castillo, N., Cormand, B. (2024) Pleiotropic contribution of rbfox1 to psychiatric and neurodevelopmental phenotypes in two zebrafish models. Translational psychiatry. 14:9999
Fontana, B.D., Reichmann, F., Tilley, C.A., Lavlou, P., Shkumatava, A., Alnassar, N., Hillman, C., Karlsson, K.Æ., Norton, W.H.J., Parker, M.O. (2023) adgrl3.1-deficient zebrafish show noradrenaline-mediated externalizing behaviors, and altered expression of externalizing disorder-candidate genes, suggesting functional targets for treatment. Translational psychiatry. 13:304304
Alnassar, N., Hillman, C., Fontana, B.D., Robson, S.C., Norton, W.H.J., Parker, M.O. (2023) angptl4 gene expression as a marker of adaptive homeostatic response to social isolation across the lifespan in zebrafish. Neurobiology of aging. 131:209221209-221
Gabellini, C., Pucci, C., De Cesari, C., Martini, D., Di Lauro, C., Digregorio, M., Norton, W., Zippo, A., Sessa, A., Broccoli, V., Andreazzoli, M. (2022) CRISPR/Cas9-Induced Inactivation of the Autism-Risk Gene setd5 Leads to Social Impairments in Zebrafish. International Journal of Molecular Sciences. 24(1):
Sveinsdóttir, H.S., Christensen, C., Þorsteinsson, H., Lavalou, P., Parker, M.O., Shkumatava, A., Norton, W.H.J., Andriambeloson, E., Wagner, S., Karlsson, K.Æ. (2022) Novel non-stimulants rescue hyperactive phenotype in an adgrl3.1 mutant zebrafish model of ADHD. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 48(8):1155-1163
Reichmann, F., Pilic, J., Trajanoski, S., Norton, W.H.J. (2022) Transcriptomic underpinnings of high and low mirror aggression zebrafish behaviours. BMC Biology. 20:97
Antón-Galindo, E., Dalla Vecchia, E., Orlandi, J.G., Castro, G., Gualda, E.J., Young, A.M.J., Guasch-Piqueras, M., Arenas, C., Herrera-Úbeda, C., Garcia-Fernàndez, J., Aguado, F., Loza-Alvarez, P., Cormand, B., Norton, W.H.J., Fernàndez-Castillo, N. (2022) Deficiency of the ywhaz gene, involved in neurodevelopmental disorders, alters brain activity and behaviour in zebrafish. Molecular psychiatry. 27(9):3739-3748
Pakdaman, Y., Denker, E., Austad, E., Norton, W.H.J., Rolfsnes, H.O., Bindoff, L.A., Tzoulis, C., Aukrust, I., Knappskog, P.M., Johansson, S., Ellingsen, S. (2021) Chip Protein U-Box Domain Truncation Affects Purkinje Neuron Morphology and Leads to Behavioral Changes in Zebrafish. Frontiers in molecular neuroscience. 14:723912
Fontana, B.D., Cleal, M., Norton, W.H.J., Parker, M.O. (2021) The impact of chronic unpredictable early-life stress (CUELS) on boldness and stress-reactivity: differential effects of stress duration and context of testing. Physiology & behavior. 240:113526
Tilley, C.A., Carreño Gutierrez, H., Sebire, M., Obasaju, O., Reichmann, F., Katsiadaki, I., Barber, I., Norton, W.H.J. (2020) Skin swabbing is a refined technique to collect DNA from model fish species. Scientific Reports. 10:18212
Fontana, B.D., Gibbon, A.J., Cleal, M., Norton, W.H.J., Parker, M.O. (2020) Chronic unpredictable early-life stress (CUELS) protocol: Early-life stress changes anxiety levels of adult zebrafish. Progress in neuro-psychopharmacology & biological psychiatry. 108:110087
Reichmann, F., Rimmer, N., Tilley, C.A., Dalla Vecchia, E., Pinion, J., Al Oustah, A., Carreño Gutiérrez, H., Young, A.M., McDearmid, J.R., Winter, M.J., Norton, W.H. (2020) The zebrafish histamine H3 receptor modulates aggression, neural activity and forebrain functional connectivity. Acta physiologica (Oxford, England). 230(4):e13543
Gutiérrez, H.C., Vacca, I., Schoenmacker, G., Cleal, M., Tochwin, A., O'Connor, B., Young, A.M.J., Vasquez, A.A., Winter, M.J., Parker, M.O., Norton, W.H.J. (2019) Screening for drugs to reduce zebrafish aggression identifies caffeine and sildenafil. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 30:17-29
Norton, W.H.J., Carreño Gutiérrez, H. (2019) Correction: The three-spined stickleback as a model for behavioural neuroscience. PLoS One. 14:e0216518
Norton, W.H.J., Carreño Gutiérrez, H. (2019) The three-spined stickleback as a model for behavioural neuroscience. PLoS One. 14:e0213320
Carreño Gutiérrez, H., Colanesi, S., Cooper, B., Reichmann, F., Young, A.M.J., Kelsh, R.N., Norton, W.H.J. (2019) Endothelin neurotransmitter signalling controls zebrafish social behaviour. Scientific Reports. 9:3040
Fontana, B.D., Franscescon, F., Rosemberg, D.B., Norton, W.H.J., Kalueff, A.V., Parker, M.O. (2019) Zebrafish models for attention deficit hyperactivity disorder (ADHD). Neuroscience and biobehavioral reviews. 100:9-18
Dalla Vecchia, E., Mortimer, N., Palladino, V.S., Kittel-Schneider, S., Lesch, K.P., Reif, A., Schenck, A., Norton, W.H.J. (2019) Cross-species models of attention-deficit/hyperactivity disorder and autism spectrum disorder: lessons from CNTNAP2, ADGRL3, and PARK2. Psychiatric genetics. 29:1-17
Norton, W.H.J., Manceau, L., Reichmann, F. (2019) The Visually Mediated Social Preference Test: A Novel Technique to Measure Social Behavior and Behavioral Disturbances in Zebrafish. Methods in molecular biology (Clifton, N.J.). 2011:121-132
Norton, W.H.J. (2018) Screening for drugs to reduce aggression in zebrafish. Neuropharmacology. 156:107394
Bitetti, A., Mallory, A.C., Golini, E., Carrieri, C., Carreño Gutiérrez, H., Perlas, E., Pérez-Rico, Y.A., Tocchini-Valentini, G.P., Enright, A.J., Norton, W.H.J., Mandillo, S., O'Carroll, D., Shkumatava, A. (2018) MicroRNA degradation by a conserved target RNA regulates animal behavior. Nature structural & molecular biology. 25(3):244-251
Gutiérrez, H.C., Vacca, I., Pons, A.I., Norton, W.H.J. (2017) Automatic quantification of juvenile zebrafish aggression. Journal of Neuroscience Methods. 296:23-31
Breacker, C., Barber, I., Norton, W.H., McDearmid, J.R., Tilley, C.A. (2017) A Low-Cost Method of Skin Swabbing for the Collection of DNA Samples from Small Laboratory Fish. Zebrafish. 14(1):35-41
Freudenberg, F., Carreño Gutierrez, H., Post, A.M., Reif, A., Norton, W.H. (2016) Aggression in non-human vertebrates: Genetic mechanisms and molecular pathways. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics. 171(5):603-40
Jones, L.J., McCutcheon, J.E., Young, A.M., Norton, W.H. (2015) Neurochemical measurements in the zebrafish brain. Frontiers in behavioral neuroscience. 9:246
Stewart, A.M., Ullmann, J.F., Norton, W.H., Parker, M.O., Brennan, C.H., Gerlai, R., Kalueff, A.V. (2015) Molecular psychiatry of zebrafish. Molecular psychiatry. 20(1):2-17
Jones, L.J., Norton, W.H. (2015) Using zebrafish to uncover the genetic and neural basis of aggression, a frequent comorbid symptom of psychiatric disorders. Behavioural brain research. 276:171-80
Lange, M., Neuzeret, F., Fabreges, B., Froc, C., Bedu, S., Bally-Cuif, L., and Norton, W.H. (2013) Inter-individual and inter-strain variations in zebrafish locomotor ontogeny. PLoS One. 8(8):e70172
Norton, W.H. (2013) Toward developmental models of psychiatric disorders in zebrafish. Frontiers in neural circuits. 7:79
Cavodeassi, F., Bene, F.D., Fürthauer, M., Grabher, C., Herzog, W., Lehtonen, S., Linker, C., Mercader, N., Mikut, R., Norton, W., Strähle, U., Tiso, N., and Foulkes, N.S. (2013) Report of the Second European Zebrafish Principal Investigator Meeting in Karlsruhe, Germany, March 21-24, 2012. Zebrafish. 10(1):119-23
Kalueff, A.V., Gebhardt, M., Stewart, A.M., Cachat, J.M., Brimmer, M., Chawla, J.S., Craddock, C., Kyzar, E.J., Roth, A., Landsman, S., Gaikwad, S., Robinson, K., Baatrup, E., Tierney, K., Shamchuk, A., Norton, W., Miller, N., Nicolson, T., Braubach, O., Gilman, C.P., Pittman, J., Rosemberg, D.B., Gerlai, R., Echevarria, D., Lamb, E., Neuhauss, S.C., Weng, W., and Bally-Cuif, L. (2013) Towards a comprehensive catalog of zebrafish behavior 1.0 and beyond. Zebrafish. 10(1):70-86
Tokarz, J., Norton, W., Möller, G., Hrabé de Angelis, M., and Adamski, J. (2013) Zebrafish 20beta-hydroxysteroid dehydrogenase type 2 is important for glucocorticoid catabolism in stress response. PLoS One. 8(1):e54851
Lange, M., Norton, W., Coolen, M., Chaminade, M., Merker, S., Proft, F., Schmitt, A., Vernier, P., Lesch, K.P., and Bally-Cuif, L. (2012) The ADHD-susceptibility gene lphn3.1 modulates dopaminergic neuron formation and locomotor activity during zebrafish development. Molecular psychiatry. 17(9):946-954
Lange, M., Norton, W., Coolen, M., Chaminade, M., Merker, S., Proft, F., Schmitt, A., Vernier, P., Lesch, K.P., and Bally-Cuif, L. (2012) The ADHD-linked gene Lphn3.1 controls locomotor activity and impulsivity in zebrafish. Molecular psychiatry. 17(9):855
Tokarz, J., Mindnich, R., Norton, W., Möller, G., Hrabé de Angelis, M., and Adamski, J. (2012) Discovery of a novel enzyme mediating glucocorticoid catabolism in fish: 20beta-Hydroxysteroid dehydrogenase type 2. Molecular and Cellular Endocrinology. 349(2):202-13
Amir-Zilberstein, L., Blechman, J., Sztainberg, Y., Norton, W.H., Reuveny, A., Borodovsky, N., Tahor, M., Bonkowsky, J.L., Bally-Cuif, L., Chen, A., and Levkowitz, G. (2012) Homeodomain protein otp and activity-dependent splicing modulate neuronal adaptation to stress. Neuron. 72(2):279-291
Norton, W.H.J., and Bally-Cuif, L. (2012) Unravelling the proximate causes of the aggression-boldness behavioural syndrome in zebrafish. Behaviour. 149:1063-1079
Kalueff, A.V., Stewart, A.M., Kyzar, E.J., Cachat, J., Gebhardt, M., Landsman, S., Robinson, K., Maximino, C., Herculano, A.M., Jesuthasan, S., Wisenden, B., Bally-Cuif, L., Lange, M., Vernier, P., Norton, W., Tierney, K., Tropepe, V., and Neuhauss, S. (2012) Time to recognize zebrafish ‘affective’ behavior. Behaviour. 149:1019-1036
Norton, W.H., Stumpenhorst, K., Faus-Kessler, T., Folchert, A., Rohner, N., Harris, M.P., Callebert, J., and Bally-Cuif, L. (2011) Modulation of Fgfr1a Signaling in Zebrafish Reveals a Genetic Basis for the Aggression-Boldness Syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience. 31(39):13796-13807
Norton, W., and Bally-Cuif, L. (2010) Adult zebrafish as a model organism for behavioural genetics. BMC Neuroscience. 11:90
Webb, K.J., Norton, W.H.J., Trumbach, D., Meijer, A.H., Ninkovic, J., Topp, S., Heck, D., Marr, C., Wurst, W., Theis, F.J., Spaink, H.P., and Bally-Cuif, L. (2009) Zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine. Genome biology. 10(7):R81
Norton, W.H., Folchert, A., and Bally-Cuif, L. (2008) Comparative analysis of serotonin receptor (HTR1A/HTR1B families) and transporter (slc6a4a/b) gene expression in the zebrafish brain. The Journal of comparative neurology. 511(4):521-542
Blin, M., Norton, W., Bally-Cuif, L., and Vernier, P. (2008) NR4A2 controls the differentiation of selective dopaminergic nuclei in the zebrafish brain. Molecular and cellular neurosciences. 39(4):592-604
Lecaudey, V., Cakan-Akdogan, G., Norton, W.H., and Gilmour, D. (2008) Dynamic Fgf signaling couples morphogenesis and migration in the zebrafish lateral line primordium. Development (Cambridge, England). 135(16):2695-2705
Dong, P.D., Munson, C.A., Norton, W., Crosnier, C., Pan, X., Gong, Z., Neumann, C.J., and Stainier, D.Y. (2007) Fgf10 regulates hepatopancreatic ductal system patterning and differentiation. Nature Genetics. 39(3):397-402
Norton, W.H., Ledin, J., Grandel, H., and Neumann, C.J. (2005) HSPG synthesis by zebrafish Ext2 and Extl3 is required for Fgf10 signalling during limb development. Development (Cambridge, England). 132(22):4963-4973
Stadler, J.A., Shkumatava, A., Norton, W.H., Rau, M.J., Geisler, R., Fischer, S., and Neumann, C.J. (2005) Histone deacetylase 1 is required for cell cycle exit and differentiation in the zebrafish retina. Developmental Dynamics : an official publication of the American Association of Anatomists. 233(3):883-889
Norton, W.H., Mangoli, M., Lele, Z., Pogoda, H.M., Diamond, B., Mercurio, S., Russell, C., Teraoka, H., Stickney, H.L., Rauch, G.J., Heisenberg, C.P., Houart, C., Schilling, T.F., Frohnhoefer, H.G., Rastegar, S., Neumann, C.J., Gardiner, R.M., Strähle, U., Geisler, R., Rees, M., Talbot, W.S., and Wilson, S.W. (2005) Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphe neurones and cranial motoneurones. Development (Cambridge, England). 132(4):645-658
Norton, W.H., Rohr, K.B., and Burnstock, G. (2000) Embryonic expression of a P2X3 receptor encoding gene in zebrafish. Mechanisms of Development. 99(1-2):149-152