AADC
Please see the JBrowse view of Dmel\Ddc for information on other features
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AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.
Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.52
2.3, 2.0 (northern blot)
4.6, 4.05, 2.95, 2.75, 2.22, 2.14, 2.10, 1.92, 1.75 (northern blot)
2.1 (northern blot)
56 (kD observed)
510, 502 (aa); 56.7, 56.2 (kD predicted)
60 (kD observed)
Homodimer.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Ddc using the Feature Mapper tool.
Ddc labels serotonergic neurons and expression is more widespread than that seen with Scer\GAL45-HT7.ERGP which labels a serotonergic receptor. Expression of Ddc is seen in subsets of cells in the larval brain and ventral nerve cord. In the adult, labelling is widespread but stronger in the central complex, including the ring neurons of the ellipsoid body, the lateral triangles (bulbs) and the fan-shaped body. Co-localisation of Ddc with Scer\GAL45-HT7.ERGP is observed in the central complex. There is also Ddc staining in 2 centrifugal neurons which innervate most of the antennal lobe glomeruli. These neurons do not express Scer\GAL45-HT7.ERGP. Ddc is also observed in all thoracic and abdominal neuromeres of the thoracico-abdominal ganglion, with stronger expression in the abdominal neuromeres.
Ddc protein is expressed in a subset of serotonergic neurons of the adult brain, including the mushroom body dorsal paired medial neurons.
Markers that uniquely identify the cells of the NB3-7 lineage were used to examine the serotonin expressing cell lineages.
Ddc activity was investigated in whole imagos and in developing wings. In the whole imago, activity increases steadily between 64 hours after pupariation and eclosion. In wings, there is a peak of activity at 76 hrs which correlates with the time when the wing microchaetae and hairs have become fully melanized.
In third instar larvae, Ddc protein localizes to approximately 125 neurons, and a subset of glial cells. About 80 of the 125 neurons also stain for serotonin.
Immunolocalization experiments using an anti-Ddc antibody indicate that Ddc protein is expressed in the epidermis and the nervous system of the third instar larva and adult. A segmentally repeated pattern of staining is seen in the larval ventral ganglion and brain. A subset of the Ddc-positive cells match the pattern of serotonin-containing cells. The staining in the adult hindgut and oviduct is likely to be due neurons associated with these structures.
Ddc activity reaches a maximum late in embryogenesis and persists into first instar larvae. It does not parallel ecdysone activity which is at a maximum at midembryogenesis.
Ddc protein enzymatic activity levels rise during late larval stages, are highest during the pre-pupal stage of development, and rise again prior to ecolsion after a decrease in activity.
Comment: medium expression
Comment: faint expression
GBrowse - Visual display of RNA-Seq signals
View Dmel\Ddc in GBrowse 2Mapping based on 5/5781 recombinants.
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Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
polyclonal
Source for merge of: Ddc l(2)k02104
Temporal profile of gene expression is altered in Eip74EF mutant background.
Hormonal induction of Ddc in the epidermis is mediated by genes of the Broad complex.
Located between coordinates +0.1 and +4.1.
Ecdysteroid-regulated gene.
65kb around Ddc used in a study that showed that restriction site distribution shows no departure from that expected under the equilibrium model, but insertions and deletions are rarer than predicted indicating that they are deleterious. Variation in level of Ddc activity is twofold from the highest to the lowest, and restriction enzyme patterns are linked to particular activities.
Profile of zfh2 expression in the larval CNS shows intriguing overlap with Ddc expression in specific serotonin and dopamine neurons. In vitro mutagenesis of the Ddc 5' region dissected the functional redundancy of two serotonin response regulatory regions. The product of zfh2 binds to a protein binding site in the Ddc promoter.
Comparison of CpG distribution in the coding region of 121 genes from six species supports the mCpG mutational hotspot explanation of CpG suppression in methylated species at position II-III and III-I.
Derepression of Ddc expression in the glia cells requires the presence of promoter sequences -209 to -25.
Genetic mosaics were used to determine the distribution of Ddc and 5HT. Phenotypic mosaicism was observed for both Ddc and 5HT immunoreactivity. Ddc neurons were always 5HT neurons, but some 5HT neurons were devoid of Ddc activity, though were always found in close proximity to other Ddc neurons. Results suggest that in vivo uptake mechanisms are responsible for 5HT accumulation in the neurons devoid of Ddc immunoreactivity.
Ddc sequences upstream of -2200bp are not required for normal neuronal expression but deletion to -760bp causes a near total loss of neuron specific expression. Hypoderm Ddc activity remains unchanged. A distal regulatory element has been identified extending from -1019 to -1623 bp. The region possesses enhancer-like properties and is essential for normal neuron-specific expression.
Element I of the Ddc promoter is responsible for stimulating Ddc expression in the CNS, but Ecol\lacZ reporter gene constructs demonstrate that it is not sufficient alone to confer CNS expression on an heterologous promoter.
Ddc affects cuticle formation.
Ddc and amd share extensive sequence homology and are the products of a gene duplication event. Dot matrix analysis demonstrates there is very little sequence homology between Ddc or amd, and l(2)37Cc or CG10561 transcripts.
Mutant alleles are useful as markers in clonal analysis.
Genetic and immunological evidence suggest that Ddc gene product is required for cuticle sclerotization during late embryogenesis and the early first larval instar.
Of 16 Ddc alleles tested, none show dominant hypersensitivity to α-methyl dopa.
Ddc is required for female fertility and the requirement is ovary-autonomous.
Ddc mutant alleles do not give rise to a dominant α-MD hypersensitive phenotype.
Structural gene for dopa decarboxylase (DDC, 3-4-dihydroxy-L-phenylalanine-carboxylase) which catalyzes the decarboxylation of dopa to dopamine (Lunan and Mitchell, 1969) and 5-hydroxytryptophan to serotonin (5-hydroxytryptamine) but not tyrosine to tyramine (Livingstone and Tempel, 1983). Native DDC isolated from mature larvae is a homodimer with subunit molecular weight 54kD (Clark et al., 1978). Distinct DDC isoforms are generated in the CNS and hypoderm by alternate splicing of the Ddc primary transcript; the CNS isoform differs by the addition of 35 amino acids at the amino terminus (Morgan, Johnson and Hirsh, 1986). The predicted subunit molecular weights of these are 57.1 and 53.4kD, respectively. DDC requires pyridoxal-5-phosphate for activity and is strongly inhibited by heavy-metal ions and the sulfhydryl reagent, N-ethylmaleimide. Initial velocity constants determined by Black and Smarrelli (1986). The dopamine produced by DDC is necessary to effect sclerotization of the cuticle, being further metabolized both to N-acetyldopamine and N-β-alanyldopamine, which after oxidation to their respective quinones, crosslink cuticular proteins. Thus in adults and white prepupae more than 90% of the DDC activity is located in the epidermis (Lunan and Mitchell, 1969; Scholnick, Morgan and Hirsh, 1983). Some DDC activity (about 5%) is found in the central nervous system of white prepupae and adults where it produces the neurotransmitters dopamine and serotonin (Wright, 1977; Livingstone and Tempel, 1983; White and Valles, 1985). The limited amounts found in the ovaries (Wright, Steward, Bentley and Adler, 1981) and proventriculus (Wright and Wright, 1978) are localized in associated neural ganglia (Konrad and Marsh, 1987). Five peaks of DDC activity evident during development: at the end of embryogenesis, the two larval molts, pupariation and eclosion (Marsh and Wright, 1980; Kraminsky et al., Sage, O'Conner and Hodgetts, 1980). The largest peak, which occurs at pupariation, is induced by a coincident ecdysone peak of the molting larvae (Marsh and Wright, 1980) and has been shown to be attributable to a rapid increase in translatable DDC mRNA following administration of 20-0H-ecdysone (Kraminsky et al., 1980). Ecdysone induces Ddc expression in the mature larval epidermis within two to four hrs (Karminsky et al., 1980; Clark et al., 1986). Since cycloheximide addition is sufficient to largely abolish this induction, it appears that this response is an indirect action of ecdysone. A different response of Ddc to ecdysone occurs in cultured imaginal discs; Ddc induction occurs only subsequent to withdrawal of the hormone (Clark et al., 1986). Most mutations in Ddc are homozygous or hemizygous lethal. The effective lethal phases of the first eight lethal alleles, Ddc1-Ddc8, were almost identical. As hemizygotes over Df(2L)TW130 almost all mortality is late embryonic with actively moving larvae, exhibiting unpigmented cephalopharyngeal apparatuses and denticle belts, unable to hatch. When homozygous there is a fairly uniform shift in effective lethal phases with mean mortalities from all eight alleles in the cross of Ddcn/CyO x Ddcn/cn bw being 13.6% embryonic, 14.1% larval and 4.8% pupal (Wright and Wright, 1978). Many larvae hemizygous for lethal alleles, or homozygous deficient for Ddc, when mechanically released from the egg membranes, continue development to the 3rd larval instar and to the pharate adult stage. Genotypes which produce individuals with drastically reduced DDC activities (about 0.5-5% of wild type) exhibit an 'escaper' phenotype characterized by incomplete pigmentation and sclerotization of the cuticle; developmental time can be prolonged for as many as four or five days; puparia are easily scored showing melanization at each end of the greenish-gray pupa case; adults often die or get stuck in the food within 24 hr of eclosion; macrochaetae may be very thin, long and straw-colored or colorless; the whole body remains light, i.e., doesn't take on its normal pigmentation; abdominal markings are apparent but do not darken; upon aging a few hours wing axillae become melanized similar to the phenotype of sp, leg joints also become melanized perhaps due to the phenoloxidase wound reaction brought on by ruptures of weakened cuticle; flies walk on tibias rather than tarsi, but leg movements appear to be coordinated (Wright, Bewley and Sherald, 1976). Genotypes that produce flies exhibiting the 'escaper' phenotype include heteroallelic intragenic complementing heterozygotes with less than 5% of the expected number of survivors (Wright, Bewley and Sherald, 1976), hemizygotes of the temperature-sensitive allele Ddcts2 raised continuously at 22oC or 25oC, or homozygotes for Ddcts1 or Ddcts2 exposed to the restrictive temperature 30oC for 24- or 48-hour pulses at the end of the pupal stage (Wright). Ddc temperature-sensitive mutants have been reported to show reduced lea
Wright, 1974.
