Genomes and Genes
Gene Symbol: th
Description: tyrosine hydroxylase
Alias: tyrosine 3-monooxygenase, th1
- Del Giacco L, Sordino P, Pistocchi A, Andreakis N, Tarallo R, Di Benedetto B, et al. Differential regulation of the zebrafish orthopedia 1 gene during fate determination of diencephalic neurons. BMC Dev Biol. 2006;6:50 pubmed..The latter structure is characterized by Tyrosine Hydroxylase (TH)-positive cells, suggesting a role for otp1 in the lineage restriction of catecholaminergic (CA) neurons...
- Fernandes A, Fero K, Arrenberg A, Bergeron S, Driever W, Burgess H. Deep brain photoreceptors control light-seeking behavior in zebrafish larvae. Curr Biol. 2012;22:2042-7 pubmed publisher..Our findings shed light on the identity and function of deep brain photoreceptors and suggest that otpa specifies an ancient population of sensory neurons that mediate behavioral responses to light. ..
- Jeong J, Einhorn Z, Mercurio S, Lee S, Lau B, Mione M, et al. Neurogenin1 is a determinant of zebrafish basal forebrain dopaminergic neurons and is regulated by the conserved zinc finger protein Tof/Fezl. Proc Natl Acad Sci U S A. 2006;103:5143-8 pubmed..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. ..
- Filippi A, Mahler J, Schweitzer J, Driever W. Expression of the paralogous tyrosine hydroxylase encoding genes th1 and th2 reveals the full complement of dopaminergic and noradrenergic neurons in zebrafish larval and juvenile brain. J Comp Neurol. 2010;518:423-38 pubmed publisher..at the base of teleost evolution resulted in two paralogous zebrafish tyrosine hydroxylase-encoding genes, th1 and th2, the expression of which has been described previously only for th1...
- Rink E, Wullimann M. Development of the catecholaminergic system in the early zebrafish brain: an immunohistochemical study. Brain Res Dev Brain Res. 2002;137:89-100 pubmedTyrosine hydroxylase-containing cells (TH cells) were investigated immunohistochemically in early and late postembryonic zebrafish brain sections (at 2 and 5 days postfertilization [dpf]) yielding an improved neuroanatomical resolution of ..
- Guo S, Brush J, Teraoka H, Goddard A, Wilson S, Mullins M, et al. Development of noradrenergic neurons in the zebrafish hindbrain requires BMP, FGF8, and the homeodomain protein soulless/Phox2a. Neuron. 1999;24:555-66 pubmed..These findings suggest that Phox2a coordinates the specification of LC in part through the induction of Phox2b and in response to cooperating signals that operate along the mediolateral and anteroposterior axes of the neural plate. ..
- Bretaud S, Allen C, Ingham P, Bandmann O. p53-dependent neuronal cell death in a DJ-1-deficient zebrafish model of Parkinson's disease. J Neurochem. 2007;100:1626-35 pubmed..Our study demonstrates the utility of zebrafish as a new animal model to study PD gene defects and suggests that modulation of downstream mechanisms, such as p53 inhibition, may be of therapeutic benefit. ..
- Lucas M, Muller F, Rüdiger R, Henion P, Rohrer H. The bHLH transcription factor hand2 is essential for noradrenergic differentiation of sympathetic neurons. Development. 2006;133:4015-24 pubmed..The expression of the noradrenergic marker genes th and dbh is strongly reduced, as well as the transcription factors gata2 and tfap2a (Ap-2alpha)...
- Sheng D, Qu D, Kwok K, Ng S, Lim A, Aw S, et al. Deletion of the WD40 domain of LRRK2 in Zebrafish causes Parkinsonism-like loss of neurons and locomotive defect. PLoS Genet. 2010;6:e1000914 pubmed publisher..Taken together, our results demonstrate that zLRRK2 is an ortholog of hLRRK2 and that the deletion of WD40 domain of zLRRK2 provides a disease model for PD. ..
- Kastenhuber E, Kratochwil C, Ryu S, Schweitzer J, Driever W. Genetic dissection of dopaminergic and noradrenergic contributions to catecholaminergic tracts in early larval zebrafish. J Comp Neurol. 2010;518:439-58 pubmed publisher..These findings are consistent with a hypothesis that Otp-dependent dopaminergic neurons establish the major modulatory system for somatomotor and somatosensory circuits in larval fish. ..
- Stewart R, Arduini B, Berghmans S, George R, Kanki J, Henion P, et al. Zebrafish foxd3 is selectively required for neural crest specification, migration and survival. Dev Biol. 2006;292:174-88 pubmed
- Holzschuh J, Hauptmann G, Driever W. Genetic analysis of the roles of Hh, FGF8, and nodal signaling during catecholaminergic system development in the zebrafish brain. J Neurosci. 2003;23:5507-19 pubmed..In summary, our results do not support the previously suggested dominant roles for sonic hedgehog and Fgf8 in specification of the first catecholaminergic neurons, but instead indicate a novel role for Nodal signaling in this process. ..
- Baulac S, Lu H, Strahle J, Yang T, Goldberg M, Shen J, et al. Increased DJ-1 expression under oxidative stress and in Alzheimer's disease brains. Mol Neurodegener. 2009;4:12 pubmed publisher..Therefore, our results strongly suggest that DJ-1 expression is not necessary during zebrafish development but can be induced in zebrafish exposed to oxidative stress and is present in human AD brains. ..
- Xi Y, Ryan J, Noble S, Yu M, Yilbas A, Ekker M. Impaired dopaminergic neuron development and locomotor function in zebrafish with loss of pink1 function. Eur J Neurosci. 2010;31:623-33 pubmed publisher..These results indicate that normal PINK1 function during development is necessary for the proper positioning of populations of dopaminergic neurons and for the establishment of neuronal circuits in which they are implicated. ..
- Tay T, Ronneberger O, Ryu S, Nitschke R, Driever W. Comprehensive catecholaminergic projectome analysis reveals single-neuron integration of zebrafish ascending and descending dopaminergic systems. Nat Commun. 2011;2:171 pubmed..The catecholaminergic projectome map provides a framework to understand the evolution and function of these neuromodulatory systems. ..
- Steele S, Ekker M, Perry S. Interactive effects of development and hypoxia on catecholamine synthesis and cardiac function in zebrafish (Danio rerio). J Comp Physiol B. 2011;181:527-38 pubmed publisher..Zebrafish (Danio rerio) possess two non-allelic TH coding genes, TH1 and TH2...
- Chandrasekar G, Lauter G, Hauptmann G. Distribution of corticotropin-releasing hormone in the developing zebrafish brain. J Comp Neurol. 2007;505:337-51 pubmed..The widespread distribution of CRH-synthesizing cells outside the preoptic region suggests additional functions of CRH in the embryonic zebrafish brain. ..
- Ryu S, Mahler J, Acampora D, Holzschuh J, Erhardt S, Omodei D, et al. Orthopedia homeodomain protein is essential for diencephalic dopaminergic neuron development. Curr Biol. 2007;17:873-80 pubmed..Thus, Otp is one of the few known transcription factors that can determine aspects of the dopaminergic phenotype and the first known factor to control the development of the diencephalospinal dopaminergic system. ..
- Zhu S, Lee J, Guo F, Shin J, Perez Atayde A, Kutok J, et al. Activated ALK collaborates with MYCN in neuroblastoma pathogenesis. Cancer Cell. 2012;21:362-73 pubmed publisher..Coexpression of activated ALK with MYCN provides prosurvival signals that block this apoptotic response and allow continued expansion and oncogenic transformation of hyperplastic neuroblasts, thus promoting progression to neuroblastoma...
- Ren G, Xin S, Li S, Zhong H, Lin S. Disruption of LRRK2 does not cause specific loss of dopaminergic neurons in zebrafish. PLoS ONE. 2011;6:e20630 pubmed publisher..Our study suggests that function of LRRK2 and its usefulness to generate zebrafish PD model needs further evaluation. ..
- McKinley E, Baranowski T, Blavo D, Cato C, Doan T, Rubinstein A. Neuroprotection of MPTP-induced toxicity in zebrafish dopaminergic neurons. Brain Res Mol Brain Res. 2005;141:128-37 pubmed..Effects on swimming behavior and touch response that result from MPTP damage are partially ameliorated by both l-deprenyl and DAT knockdown. ..
- Lam C, Korzh V, Strahle U. Zebrafish embryos are susceptible to the dopaminergic neurotoxin MPTP. Eur J Neurosci. 2005;21:1758-62 pubmed
- Liu F, Pogoda H, Pearson C, Ohyama K, L hr H, Hammerschmidt M, et al. Direct and indirect roles of Fgf3 and Fgf10 in innervation and vascularisation of the vertebrate hypothalamic neurohypophysis. Development. 2013;140:1111-22 pubmed publisher..Together, our studies suggest a model for the integrated neurohemal wiring of the hypothalamo-neurohypophyseal axis...
- Wen L, Wei W, Gu W, Huang P, Ren X, Zhang Z, et al. Visualization of monoaminergic neurons and neurotoxicity of MPTP in live transgenic zebrafish. Dev Biol. 2008;314:84-92 pubmed publisher..The GFP positive neurons include the large and pear-shaped tyrosine hydroxylase positive neurons (TH populations 2 and 4) in the posterior tuberculum of ventral diencephalon (PT neurons), which are thought to be ..
- Candy J, Collet C. Two tyrosine hydroxylase genes in teleosts. Biochim Biophys Acta. 2005;1727:35-44 pubmed..Barramundi TH1 is the homologue of the higher vertebrate TH genes and encodes a protein of 489 amino acids that shares 90% ..
- Chen Y, Priyadarshini M, Panula P. Complementary developmental expression of the two tyrosine hydroxylase transcripts in zebrafish. Histochem Cell Biol. 2009;132:375-81 pubmed publisher..We cloned them and studied their expression in zebrafish. In adult tissues, th1 mRNA was more abundant than th2 mRNA in the brain and eyes, whereas th2 mRNA was more abundant in the liver, kidney,..
- Löhr H, Ryu S, Driever W. Zebrafish diencephalic A11-related dopaminergic neurons share a conserved transcriptional network with neuroendocrine cell lineages. Development. 2009;136:1007-17 pubmed publisher..Our data suggest a common evolutionary origin of specific hypothalamic neuroendocrine and dopaminergic systems. ..
- Yamamoto K, Ruuskanen J, Wullimann M, Vernier P. Two tyrosine hydroxylase genes in vertebrates New dopaminergic territories revealed in the zebrafish brain. Mol Cell Neurosci. 2010;43:394-402 pubmed publisher..Two TH genes (TH1 and TH2) have been reported to exist in the genome of some teleost fishes, TH1 being orthologous to the mammalian ..
- Russek Blum N, Gutnick A, Nabel Rosen H, Blechman J, Staudt N, Dorsky R, et al. Dopaminergic neuronal cluster size is determined during early forebrain patterning. Development. 2008;135:3401-13 pubmed publisher..This study also shows, for the first time, that diencephalic DA population size is modulated inside the neural plate much earlier than expected, concomitant with Wnt-mediated regional patterning events. ..
- Filippi A, Durr K, Ryu S, Willaredt M, Holzschuh J, Driever W. Expression and function of nr4a2, lmx1b, and pitx3 in zebrafish dopaminergic and noradrenergic neuronal development. BMC Dev Biol. 2007;7:135 pubmed..A di-mesencephalic longitudinal domain of lmx1b expression may be the basis for the expansion and posterior shift of ventral di-/mesencephalic dopaminergic populations with ascending projections during evolution. ..
- Son O, Kim H, Ji M, Yoo K, Rhee M, Kim C. Cloning and expression analysis of a Parkinson's disease gene, uch-L1, and its promoter in zebrafish. Biochem Biophys Res Commun. 2003;312:601-7 pubmed..These results suggest that uch-L1 may have an important role in the development of neuronal cells in early embryos as well as in the degeneration and disease of neuronal cells in late adult brain. ..
- Fernandes A, Beddows E, Filippi A, Driever W. Orthopedia transcription factor otpa and otpb paralogous genes function during dopaminergic and neuroendocrine cell specification in larval zebrafish. PLoS ONE. 2013;8:e75002 pubmed publisher..for null alleles of otpa, otpb, or both genes to determine their individual contributions to the specification of th expressing dopaminergic neuronal populations as well as of crh, oxt, avp, trh or sst1...
- Fett M, Pilsl A, Paquet D, van Bebber F, Haass C, Tatzelt J, et al. Parkin is protective against proteotoxic stress in a transgenic zebrafish model. PLoS ONE. 2010;5:e11783 pubmed publisher..In order to study the function of parkin in more detail and to address possible differences in its role in different species, we chose Danio rerio as a different vertebrate model system...
- Prober D, Rihel J, Onah A, Sung R, Schier A. Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish. J Neurosci. 2006;26:13400-10 pubmed
- Ettl A, Holzschuh J, Driever W. The zebrafish mutation m865 affects formation of dopaminergic neurons and neuronal survival, and maps to a genetic interval containing the sepiapterin reductase locus. Anat Embryol (Berl). 2006;211 Suppl 1:73-86 pubmed
- Suen M, Chan W, Hung K, Chen Y, Mo Z, Yung K. Assessments of the effects of nicotine and ketamine using tyrosine hydroxylase-green fluorescent protein transgenic zebrafish as biosensors. Biosens Bioelectron. 2013;42:177-85 pubmed publisher..study, plasmid constructs containing green fluorescent protein (GFP) and the promoter of tyrosine hydroxylase (TH), a key synthetic enzyme for catecholamines, were produced...
- Boisset G, Schorderet D. Zebrafish hmx1 promotes retinogenesis. Exp Eye Res. 2012;105:34-42 pubmed publisher..However, the key patterning genes tested so far were not regulated by hmx1. Altogether, these results suggest an important role for hmx1 in retinogenesis. ..
- Zu Y, Tong X, Wang Z, Liu D, Pan R, Li Z, et al. TALEN-mediated precise genome modification by homologous recombination in zebrafish. Nat Methods. 2013;10:329-31 pubmed publisher..effector nuclease mRNAs and a donor vector with long homologous arms targeting the tyrosine hydroxylase (th) locus, and we observed effective gene modification that was transmitted through the germ line...
- Damm E, Clements W. Pdgf signalling guides neural crest contribution to the haematopoietic stem cell specification niche. Nat Cell Biol. 2017;19:457-467 pubmed publisher..Preventing association of the NC with the DA leads to loss of HSCs. Our results define NC as key cellular components of the HSC specification niche that can be profiled to identify unknown HSC specification signals. ..
- Pei D, Luther W, Wang W, Paw B, Stewart R, George R. Distinct neuroblastoma-associated alterations of PHOX2B impair sympathetic neuronal differentiation in zebrafish models. PLoS Genet. 2013;9:e1003533 pubmed publisher..deficiency, modeled by phox2b morpholino knockdown, led to a decrease in the terminal differentiation markers th and dbh in sympathetic ganglion cells...
- Elbaz I, Yelin Bekerman L, Nicenboim J, Vatine G, Appelbaum L. Genetic ablation of hypocretin neurons alters behavioral state transitions in zebrafish. J Neurosci. 2012;32:12961-72 pubmed publisher..Our results further suggest a key role of HCRT neurons in mediating behavioral state transitions in response to external stimuli. ..
- Darland T, Mauch J, Meier E, Hagan S, Dowling J, Darland D. Sulpiride, but not SCH23390, modifies cocaine-induced conditioned place preference and expression of tyrosine hydroxylase and elongation factor 1? in zebrafish. Pharmacol Biochem Behav. 2012;103:157-67 pubmed publisher..Acute cocaine exposure also induced a rise in the expression of tyrosine hydroxylase (TH), an important enzyme in dopamine synthesis, and a significant decrease in the expression of elongation factor 1? (..
- Soman S, Keatinge M, Moein M, Da Costa M, Mortiboys H, Skupin A, et al. Inhibition of the mitochondrial calcium uniporter rescues dopaminergic neurons in pink1-/- zebrafish. Eur J Neurosci. 2017;45:528-535 pubmed publisher..Our data suggest modulation of MCU-mediated mitochondrial calcium homeostasis as a possible neuroprotective strategy in PINK1 mutant PD. ..
- Boer E, Jette C, Stewart R. Neural Crest Migration and Survival Are Susceptible to Morpholino-Induced Artifacts. PLoS ONE. 2016;11:e0167278 pubmed publisher..We suggest that comparison of genetic mutants between different species is the most rigorous method for identifying conserved genetic mechanisms controlling NC development and is critical to identify new treatments for NC diseases. ..
- Tao T, Sondalle S, Shi H, Zhu S, Perez Atayde A, Peng J, et al. The pre-rRNA processing factor DEF is rate limiting for the pathogenesis of MYCN-driven neuroblastoma. Oncogene. 2017;36:3852-3867 pubmed publisher..Our results indicate that DEF and possibly other components of the SSU processome provide a novel site of vulnerability in neuroblastoma cells that could be exploited for targeted therapy. ..
- Meng S, Ryu S, Zhao B, Zhang D, Driever W, McMahon D. Targeting retinal dopaminergic neurons in tyrosine hydroxylase-driven green fluorescent protein transgenic zebrafish. Mol Vis. 2008;14:2475-83 pubmed..line of zebrafish expressing green fluorescent protein (GFP) under the control of the tyrosine hydroxylase (th1) promoter...
- Durr K, Holzschuh J, Filippi A, Ettl A, Ryu S, Shepherd I, et al. Differential roles of transcriptional mediator complex subunits Crsp34/Med27, Crsp150/Med14 and Trap100/Med24 during zebrafish retinal development. Genetics. 2006;174:693-705 pubmed
- Bräutigam L, Hillmer J, Söll I, Hauptmann G. Localized expression of urocortin genes in the developing zebrafish brain. J Comp Neurol. 2010;518:2978-95 pubmed publisher..The prominent expression of uts1 and ucn3 in brainstem is consistent with proposed roles of CRH-related peptides in stress-induced modulation of locomotor activity through monoaminergic brainstem neuromodulatory systems. ..
- Trivellin G, Bjelobaba I, Daly A, Larco D, Palmeira L, Faucz F, et al. Characterization of GPR101 transcript structure and expression patterns. J Mol Endocrinol. 2016;57:97-111 pubmed publisher..These findings suggest an important role for GPR101 in brain and pituitary development and likely reflect the very different growth, development and maturation patterns among species. ..
- Chen Y, Sundvik M, Rozov S, Priyadarshini M, Panula P. MANF regulates dopaminergic neuron development in larval zebrafish. Dev Biol. 2012;370:237-49 pubmed publisher..the two tyrosine hydroxylase gene transcripts were decreased and a decrease in neuron number in certain groups of th1 and th2 cells in the diencephalon region in MANF morphants was observed...
- Podlasz P, Sallinen V, Chen Y, Kudo H, Fedorowska N, Panula P. Galanin gene expression and effects of its knock-down on the development of the nervous system in larval zebrafish. J Comp Neurol. 2012;520:3846-62 pubmed publisher..The results suggest that galanin does not regulate the development of these key markers of specific neurons, although galanin-expressing fibers were in a close spatial proximity to several neurons of these neuronal populations. ..
- Shih D, Hsiao C, Min M, Lai W, Yang C, Lee W, et al. Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions. PLoS ONE. 2013;8:e71741 pubmed publisher..Collectively, loss of Ddc appears to result in similar phenotypes as that of ADCC deficiency, thus zebrafish could be a good model for investigating pathogenetic mechanisms of AADC deficiency in children. ..
- Jászai J, Reifers F, Picker A, Langenberg T, Brand M. Isthmus-to-midbrain transformation in the absence of midbrain-hindbrain organizer activity. Development. 2003;130:6611-23 pubmed..Taken together, our analysis reveals that cells of the isthmic and cerebellar primordia acquire a more rostral, tectal identity in the absence of the functional MHB organizer signal Fgf8. ..
- Chen Y, Semenova S, Rozov S, Sundvik M, Bonkowsky J, Panula P. A Novel Developmental Role for Dopaminergic Signaling to Specify Hypothalamic Neurotransmitter Identity. J Biol Chem. 2016;291:21880-21892 pubmed..of histamine neurons, we inhibited the translation of the two non-allelic forms of tyrosine hydroxylase (th1 and th2) in zebrafish larvae...
- Lovett Barron M, Andalman A, Allen W, Vesuna S, Kauvar I, Burns V, et al. Ancestral Circuits for the Coordinated Modulation of Brain State. Cell. 2017;171:1411-1423.e17 pubmed publisher..These experiments establish a method for unbiased discovery of cellular elements underlying behavior and reveal an evolutionarily conserved set of diverse neuromodulatory systems that collectively govern internal state. ..
- Ristori E, Lopez Ramirez M, Narayanan A, Hill Teran G, Moro A, Calvo C, et al. A Dicer-miR-107 Interaction Regulates Biogenesis of Specific miRNAs Crucial for Neurogenesis. Dev Cell. 2015;32:546-60 pubmed publisher..We propose that miR-107 modulation of dicer levels in differentiating neuronal cells is required to maintain the homeostatic levels of specific miRNAs, whose precise accumulation is essential for neurogenesis. ..
- Jang Y, Yu S, Lee E, Jeon C. Two types of tyrosine hydroxylase-immunoreactive neurons in the zebrafish retina. Neurosci Res. 2011;71:124-33 pubmed publisher..Two types of tyrosine hydroxylase-immunoreactive (TH-IR) cells appeared on the basis of dendritic morphology and stratification patterns in the inner plexiform layer (..
- Guella I, Pistocchi A, Asselta R, Rimoldi V, Ghilardi A, Sironi F, et al. Mutational screening and zebrafish functional analysis of GIGYF2 as a Parkinson-disease gene. Neurobiol Aging. 2011;32:1994-2005 pubmed publisher..These data, together with those recently reported by other groups, suggest that GIGYF2 is unlikely to be the PARK11 gene. ..
- Wang F, Chen X, Shi W, Yao L, Gao M, Yang Y, et al. Zdhhc15b Regulates Differentiation of Diencephalic Dopaminergic Neurons in zebrafish. J Cell Biochem. 2015;116:2980-91 pubmed publisher..Tyrosine hydroxylase (TH) immunofluorescence of cultured DA neurons in vitro also showed that DA neurons were immature following zdhhc15b ..
- Kuscha V, Barreiro Iglesias A, Becker C, Becker T. Plasticity of tyrosine hydroxylase and serotonergic systems in the regenerating spinal cord of adult zebrafish. J Comp Neurol. 2012;520:933-51 pubmed publisher..Here we performed a quantitative study to determine the plastic changes of tyrosine hydroxylase-positive (TH1(+); mainly dopaminergic), and serotonergic (5-HT(+)) terminals and cells during successful spinal cord regeneration ..
- Kastenhuber E, Kern U, Bonkowsky J, Chien C, Driever W, Schweitzer J. Netrin-DCC, Robo-Slit, and heparan sulfate proteoglycans coordinate lateral positioning of longitudinal dopaminergic diencephalospinal axons. J Neurosci. 2009;29:8914-26 pubmed publisher..Simultaneous integrations of repulsive and attractive long-range cues from the midline act in a concerted manner to define lateral positions of DA longitudinal axon tracts. ..
- Won M, Ro H, Park H, Kim K, Huh T, Kim C, et al. Dynamic expression patterns of zebrafish 1G5 (1G5z), a calmodulin kinase-like gene in the developing nervous system. Dev Dyn. 2006;235:835-42 pubmed..In addition, bromodeoxyuridine staining further confirmed that the 1G5z-positive cells were postmitotic sensory and interneurons. ..