Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe features of the regulation of a neural-specific gene, SCG10, which is induced by nerve growth factor (NGF) during the neuronal differentiation of the rat pheochromocytoma cell line PC12. Induction of SCG10 mRNA occurs within 12-24 hr of exposure to NGF, is sustained in the continued presence of the neurotrophic factor, and involves a mechanism that is, at least in part, transcriptional. Unlike the rapid, transient transcriptional activations of genes such as c-fos, SCG10 induction requires ongoing protein synthesis, suggesting the participation of a de novo synthesized regulatory protein in mediating the effects of NGF on this gene. Although c-fos itself may play this role, its induction is clearly insufficient to cause an induction of SCG10. NGF, FGF, and, to a lesser extent, phorbol esters induced SCG10, whereas EGF and dibutyryl cAMP did not. In these characteristics, SCG10 induction appears to constitute a reliable molecular index of the transcription-dependent neuronal differentiation induced by NGF. Glucocorticoids, which inhibit NGF-induced neurite outgrowth from normal primary chromaffin cells, partially blocked SCG10 induction in PC12 cells. A reciprocal pattern of regulation by NGF and glucocorticoids was observed for tyrosine hydroxylase mRNA. These data suggest that environmental signals such as NGF may act on specific genes, both positively and negatively, to control the choice of alternative fates by developing neural crest cells.
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PMID:The induction of a neural-specific gene, SCG10, by nerve growth factor in PC12 cells is transcriptional, protein synthesis dependent, and glucocorticoid inhibitable. 283 17

Expression of mRNAs encoding the dopamine transporter (DAT) and tyrosine hydroxylase (TH) in dopaminergic neurons of the substantia nigra (SN) was examined in young and aged Fischer 344 rats by in situ hybridization. Quantitative analysis revealed a statistically significant decline in both DAT and TH mRNA expression in 24-month-old rats in comparison to 6-month-old rats. In addition, it was noted that DAT mRNA expression tended to decrease by 18 months, while TH mRNA reduction did not occur until 24 months. The age-related loss of DAT and TH mRNA expressions was accompanied by diminished expression of mRNA for a neuronal growth-associated protein GAP-43, but not for SCG10 or alpha 1-tubulin. The loss of GAP-43 mRNA became evident when both DAT and TH gene expression declined with advanced age. Our findings indicate that DAT may be a marker of atrophy in dopamine neurons during normal aging.
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PMID:Reduced expression of the molecular markers of dopaminergic neuronal atrophy in the aging rat brain. 761 30

We have examined the regulation of transcription factor gene expression and phenotypic markers in developing chick sympathetic neurons. Sympathetic progenitor cells first express the bHLH transcriptional regulator Cash-1 (a chicken achaete-scute homologue), followed by coordinate expression of Phox2, a paired homeodomain protein, and GATA-2, a zinc finger protein. SCG10, a pan-neuronal membrane protein, is first detected one stage later, followed by the catecholaminergic neurotransmitter enzyme tyrosine hydroxylase (TH). We have used these markers to ask two questions: (1) is their expression dependent upon inductive signals derived from the notochord or floor plate?; (2) does their sequential expression reflect a single linear pathway or multiple parallel pathways? Notochord ablation experiments indicate that the floor plate is essential for induction of GATA-2, Phox2 and TH, but not for that of Cash-1 and SCG10. Taken together these data suggest that the development of sympathetic neurons involves multiple transcriptional regulatory cascades: one, dependent upon notochord or floor plate-derived signals and involving Phox2 and GATA-2, is assigned to the expression of the neurotransmitter phenotype; the other, independent of such signals and involving Cash-1, is assigned to the expression of pan-neuronal properties. The parallel specification of different components of the terminal neuronal phenotype is likely to be a general feature of neuronal development.
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PMID:Differential regulation of transcription factor gene expression and phenotypic markers in developing sympathetic neurons. 772 May 91

Bone morphogenetic proteins (BMPs) induce autonomic neurogenesis in neural crest cultures and stimulate sympathetic neuron development when overexpressed in vivo. We demonstrate that inhibition of BMPs in the chick embryo bythe BMP antagonist Noggin prevents sympathetic neuron generation. In Noggin-treated embryos, the noradrenergic marker genes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), panneuronal neurofilament 160 (NF160) and SCG10 genes, and the transcriptional regulators Phox2b and Phox2a are not expressed in sympathetic ganglia. Whereas initial ganglion development is not affected, the expression of the basic helix-loop-helix transcription factor Cash-1 is strongly reduced. These results demonstrate that BMPs are essential for sympathetic neuron development and establish Cash-1 and Phox2 genes as downstream effectors of BMPs in this lineage.
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PMID:Bone morphogenetic proteins are required in vivo for the generation of sympathetic neurons. 1062 49

Bone morphogenetic protein-2 (BMP-2) promotes the development of primary neural crest cells grown in tissue culture to the sympathoadrenal (SA) lineage. Independent studies have characterized the expression patterns of SA-lineage genes in developing chicken embryo; however, studies using cultured primary neural crest cells have characterized only the expression patterns of the catecholaminergic markers, tyrosine hydroxylase (TH) and catecholamines (CAs). To further explore the molecular mechanisms that control SA-cell development using the in vitro model system, it is crucial to define the expression patterns of both the catecholaminergic markers and the genes regulating SA-lineage determination. Accordingly, we defined, in the absence and presence of BMP-2, the temporal expression patterns of TH and CA, the SA lineage-determining genes ASH-1, Phox2a, and Phox2b, the GATA-2 gene, and the pan-neuronal SCG10 gene. Comparison of these data with the reported temporal and spatial patterns of expression in vivo demonstrate that the inductive steps of SA-lineage determination, including the specification of neurotransmitter identity and neuronal fate, are recapitulated in the neural-crest culture system.
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PMID:Differential expression of sympathoadrenal lineage-determining genes and phenotypic markers in cultured primary neural crest cells. 1137 Aug 13

We have analyzed the distribution of neural crest-derived precursors and the expression of catecholaminergic and neuronal markers in developing adrenal tissue of chick embryos. Undifferentiated neural crest cells are found in presumptive adrenal regions from embryonic day 3 (E3) onward. An increasing proportion of cells expressing tyrosine hydroxylase (TH) mRNA indicates catecholaminergic differentiation of precursors not only in primary sympathetic ganglia, but also in presumptive adrenal regions. Whereas precursors and differentiating cells show mesenchymal distribution until E5, discrete adrenal anlagen form during E6. Even during E5, catecholaminergic cells with low or undetectable neurofilament M (NF-M) mRNA expression prevail in positions at which adrenal anlagen become distinct during E6. The predominance of TH-positive and NF-M-negative cells is maintained throughout embryogenesis in adrenal tissue. RNA encoding SCG10, a pan-neuronal marker like NF-M, is strongly expressed throughout adrenal anlagen during E6 but is found at reduced levels in chromaffin cells compared with neuronal cells at E15. Two additional neuronal markers, synaptotagmin 1 and neurexin 1, are expressed at low to undetectable levels in developing chromaffin cells throughout embryogenesis. The developmental regulation of neuronal markers shows at least three different patterns among the four mRNAs analyzed. Importantly, there is no generalized downregulation of neuronal markers in developing adrenal anlagen. Thus, our observations question the classical concept of chromaffin differentiation from a common sympathoadrenal progenitor expressing neuronal properties and suggest alternative models with changing instructive signals or separate progenitor populations for sympathetic neuronal and chromaffin endocrine cells.
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PMID:Expression of neuronal markers suggests heterogeneity of chick sympathoadrenal cells prior to invasion of the adrenal anlagen. 1556 70

In avian species, the ultimobranchial anlage is populated with neuronal cells derived from the distal vagal ganglion. We found that ultimobranchial C cells of chick embryos cultured in the presence of nicotinamide continued to grow for at least 60 days and exhibited profound morphological changes, resulting in the formation of dense networks of neuronal fibers. Nicotinamide, thus, facilitated the manifestation of neuronal features in C cells. The neuronal phenotypes of cultured C cells were analyzed in detail by both scanning and transmission electron microscopy. Their neural nature was also positively established by immunostaining with monoclonal antibodies to the neuronal markers neuron-specific class III beta-tubulin (TuJ1), microtubule-associated protein (MAP) 2, and synaptophysin. Confocal laser scanning microscopy confirmed that these neuron-specific proteins are colocalized with calcitonin in both the somata and the neuronal processes of C cells. Furthermore, reverse transcriptase-polymerase chain reaction analyses, performed at various times up to 30 days in culture, indicated that the C cells have persistent gene expression of calcitonin, the catecholamine-synthesizing enzyme tyrosine hydroxylase, proenkephalin, proopiomelanocortin, neuron-specific beta-tubulin (cbeta4), SCG10, and Bcl-2. The morphological responses of C cells to nicotinamide treatment were analyzed quantitatively over a period of 60 days. The area of C-cell colonies, number of processes per colony, and length of processes continued to increase until culture day 45. In conclusion, nicotinamide stimulates long-term survival and neuronal differentiation of chick embryo C cells, and this culture system may provide a useful model for studying neuronal differentiation mechanisms.
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PMID:Nicotinamide promotes long-term survival and extensive neurite outgrowth in ultimobranchial C cells cultured from chick embryos. 1621 94

The basic helix-loop-helix transcription factor Hand2 is essential for the proliferation and noradrenergic differentiation of sympathetic neuron precursors during development. Here we address the function of Hand2 in postmitotic, differentiated sympathetic neurons. Knockdown of endogenous Hand2 in cultured E12 chick sympathetic neurons by siRNA results in a significant (about 60%) decrease in the expression of the noradrenergic marker genes dopamine-beta-hydroxylase (DBH) and tyrosine hydroxylase (TH). In contrast, expression of the pan-neuronal genes TuJ1, HuC and SCG10 was not affected. To analyze the in vivo role of Hand2 in differentiated sympathetic neurons we used mice harboring a conditional Hand2-null allele and excised the gene by expression of Cre recombinase under control of the DBH promotor. Mouse embryos homozygous for Hand2 gene deletion showed decreased sympathetic neuron number and TH expression was strongly reduced in the residual neuron population. The in vitro Hand2 knockdown also enhances the CNTF-induced expression of the cholinergic marker genes vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT). Taken together, these findings demonstrate that the Hand2 transcription factor plays a key role in maintaining noradrenergic properties in differentiated neurons.
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PMID:The bHLH transcription factor Hand2 is essential for the maintenance of noradrenergic properties in differentiated sympathetic neurons. 1925 8