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Gene Review

Ddc  -  Dopa decarboxylase

Drosophila melanogaster

Synonyms: 5-HT, AADC, Aromatic-L-amino-acid decarboxylase, CG10697, DDC, ...
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Disease relevance of Ddc

  • In situ hybridization reveals the selective expression of dSERT mRNA to specific cell bodies in the ventral ganglion of the embryonic and larval Drosophila nervous system with a distribution pattern virtually identical to that of 5HT-containing neurons [1].

High impact information on Ddc

  • DDC catalyzes the final step in the synthesis of the neurotransmitters, dopamine and serotonin [2].
  • Transformants were identified by suppression of the cuticular phenotype of a Ddc mutant allele [3].
  • The reintegrated genes are expressed in the proper tissue and at the proper stages during development even though their positions within the genome are different from that of the wild-type Ddc gene [3].
  • One reintegrated Ddc gene, inserted on the X chromosome, is affected by the dosage compensation mechanism that leads to sex-specific differences in the expression of many X-chromosome genes [3].
  • For example, NTF-1 plays a critical role in the tissue-specific expression of the Drosophila Dopa decarboxylase gene [4].

Biological context of Ddc

  • Both phenotypes show tight genetic linkage to the dopa decarboxylase, Ddc, and l(2)amd genes (i.e., less than 0.05 cM distant) [5].
  • Both cytogenetic and molecular analyses indicate that these overproduction variants are not the result of small duplications of the Ddc and amd genes, nor are they associated with small (greater than or equal to 100 bp) insertions or deletions [5].
  • This suggests that in wild-type different isoforms of DDC are produced either by differences in post-translational modification or as a result of a different primary amino acid sequence.(ABSTRACT TRUNCATED AT 400 WORDS)[6]
  • Transgenes, bearing a Ddc fragment from which one of the cis-acting silencers has been deleted, exhibit beta-galactosidase reporter activity in the epidermal cells prior to the appearance of endogenous DDC [7].
  • The developmental expression of the integrated genes was examined by monitoring the embryonic induction of dopa decarboxylase enzyme activity (DDC) and by monitoring the developmental pattern of DDC activity from late third instar to eclosion [8].

Anatomical context of Ddc

  • Our demonstration that Ddc is a target of BR-C in the epidermis is the first direct evidence of a role for this early gene in a tissue other than the salivary glands [9].
  • Dopa decarboxylase (DDC) functions in insect catecholamine biochemistry to produce materials essential for cross-linking reactions that result in tanning and/or melanization, include tanning of the mosquito egg chorion and encapsulation of parasites [10].
  • All Ddc genes lacking the normal immediate 5'-flanking sequences were grossly deficient in larval central nervous system expression [11].
  • The 5-HT fibers, located in the proventriculus and midgut, were visualized immunocytochemically by using a monoclonal antibody against 5-HT [12].
  • In the mutant ventral ganglia, in the absence of DDC enzyme activity, most normal-CF neurons still exhibit CF, probably indicating the presence of accumulated L-dopa [13].

Associations of Ddc with chemical compounds

  • The in vivo profile of ZFH-2 in the larval CNS shows intriguing overlap with DDC in specific serotonin and dopamine neurons [14].
  • Exposure of the mature larval epidermis to 20-OH-ecdysone caused a rapid accumulation of DDC transcripts [15].
  • This suggests that the increased resistance to dietary alpha-methyldopa is not the result of increased DDC activity but, rather, results from increased l(2)amd+ activity [5].
  • The inferred amino acid sequence of this clone shares 81% identity with the published Drosophila Ddc cDNA, including complete identity with twenty-four contiguous amino acids encompassing the pyridoxal-5-phosphate cofactor binding domain [10].
  • Interestingly, the pyridoxal-binding peptide of porcine DDC matches the Drosophila sequence perfectly suggesting considerable selective pressure on at least portions of the sequence [16].

Physical interactions of Ddc

  • Both the transcript and a protein carrying this domain are present in the epidermis and a BR-C recombinant protein carrying the Z2 finger binds to the first intron of the Ddc gene [9].

Regulatory relationships of Ddc


Other interactions of Ddc

  • Although the adult cuticle lacks proper pigmentation as expected in flies with low DDC activity (less than or equal to 5%), the bristles unexpectedly have wild-type black pigmentation [6].
  • Untranslated 3' ends of the convergently transcribed genes Cs and Ddc are known to overlap by 88bp [18].
  • Analysis of an F2 intercross population derived from a parental cross between two Ae. aegypti strains (Hamburg and Moyo-In-Dry) allowed us to map Ddc to a locus on linkage group 2 [10].
  • Individuals heterozygous for the noncomplementing allele, Ddcn7, over the 12-band DDC deficiency, Df (2L)130, die at the end of embryogenesis as unhatched larvae with unpigmented mouth parts [19].
  • This effect is specific to 5-HT fibers, since glutamate-like and FMRFamide-like immunoreactive fibers of the proventriculus and midgut remain unaffected in the mutant [12].

Analytical, diagnostic and therapeutic context of Ddc

  • We find that low (Oregon-R), medium (RS) and high (RE and Canton-S) levels of DDC activity seen at both pupariation and eclosion in these strains are completely accounted for by differences in accumulation of DDC protein as measured by immunoprecipitation [5].
  • CNSs of wild-type larvae and of larvae genetically deficient for the gene Ddc were processed for serotonin immunocytochemistry using a monoclonal antibody against 5HT [20].
  • The northern blotting revealed nine DDC transcript species were present during embryogenesis and hybridization to intron-specific probes indicated that five of these contained at least part of one (or both) of the two introns [21].
  • We characterized genomic clones derived from the rat AADC locus by Southern blot and nucleotide sequencing analyses to explore the exonal organization of the gene [22].
  • We used complementation tests of deficiencies to fine map these QTL to 12 chromosomal regions and complementation tests of mutations to identify 13 positional candidate genes affecting locomotor reactivity, including Dopa decarboxylase (Ddc), which catalyzes the final step in the synthesis of serotonin and dopamine [23].


  1. Cloning, expression, and localization of a chloride-facilitated, cocaine-sensitive serotonin transporter from Drosophila melanogaster. Demchyshyn, L.L., Pristupa, Z.B., Sugamori, K.S., Barker, E.L., Blakely, R.D., Wolfgang, W.J., Forte, M.A., Niznik, H.B. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. Dopa decarboxylase (Ddc) affects variation in Drosophila longevity. De Luca, M., Roshina, N.V., Geiger-Thornsberry, G.L., Lyman, R.F., Pasyukova, E.G., Mackay, T.F. Nat. Genet. (2003) [Pubmed]
  3. The cloned dopa decarboxylase gene is developmentally regulated when reintegrated into the Drosophila genome. Scholnick, S.B., Morgan, B.A., Hirsh, J. Cell (1983) [Pubmed]
  4. Drosophila tissue-specific transcription factor NTF-1 contains a novel isoleucine-rich activation motif. Attardi, L.D., Tjian, R. Genes Dev. (1993) [Pubmed]
  5. Evidence for regulatory variants of the dopa decarboxylase and alpha-methyldopa hypersensitive loci in Drosophila. Marsh, J.L., Wright, T.R. Genetics (1986) [Pubmed]
  6. DdcDE1, a mutant differentially affecting both stage and tissue specific expression of dopa decarboxylase in Drosophila. Bishop, C.P., Wright, T.R. Genetics (1987) [Pubmed]
  7. Control of Dopa decarboxylase gene expression by the Broad-Complex during metamorphosis in Drosophila. Chen, L., O'Keefe, S.L., Hodgetts, R.B. Mech. Dev. (2002) [Pubmed]
  8. Developmental control of transduced dopa decarboxylase genes in D. melanogaster. Marsh, J.L., Gibbs, P.D., Timmons, P.M. Mol. Gen. Genet. (1985) [Pubmed]
  9. Hormonal induction of Dopa decarboxylase in the epidermis of Drosophila is mediated by the Broad-Complex. Hodgetts, R.B., Clark, W.C., O'Keefe, S.L., Schouls, M., Crossgrove, K., Guild, G.M., von Kalm, L. Development (1995) [Pubmed]
  10. Mosquito dopa decarboxylase cDNA characterization and blood-meal-induced ovarian expression. Ferdig, M.T., Li, J., Severson, D.W., Christensen, B.M. Insect Mol. Biol. (1996) [Pubmed]
  11. Delimiting regulatory sequences of the Drosophila melanogaster Ddc gene. Hirsh, J., Morgan, B.A., Scholnick, S.B. Mol. Cell. Biol. (1986) [Pubmed]
  12. Altered branching of serotonin-containing neurons in Drosophila mutants unable to synthesize serotonin and dopamine. Budnik, V., Wu, C.F., White, K. J. Neurosci. (1989) [Pubmed]
  13. Perturbed pattern of catecholamine-containing neurons in mutant Drosophila deficient in the enzyme dopa decarboxylase. Budnik, V., Martin-Morris, L., White, K. J. Neurosci. (1986) [Pubmed]
  14. The zfh-2 gene product is a potential regulator of neuron-specific dopa decarboxylase gene expression in Drosophila. Lundell, M.J., Hirsh, J. Dev. Biol. (1992) [Pubmed]
  15. Differential responses of the dopa decarboxylase gene to 20-OH-ecdysone in Drosophila melanogaster. Clark, W.C., Doctor, J., Fristrom, J.W., Hodgetts, R.B. Dev. Biol. (1986) [Pubmed]
  16. Sequence and structure of the dopa decarboxylase gene of Drosophila: evidence for novel RNA splicing variants. Eveleth, D.D., Gietz, R.D., Spencer, C.A., Nargang, F.E., Hodgetts, R.B., Marsh, J.L. EMBO J. (1986) [Pubmed]
  17. Insights into the molecular basis of the hormonal control of molting and metamorphosis from Manduca sexta and Drosophila melanogaster. Riddiford, L.M., Hiruma, K., Zhou, X., Nelson, C.A. Insect Biochem. Mol. Biol. (2003) [Pubmed]
  18. A compact gene cluster in Drosophila: the unrelated Cs gene is compressed between duplicated amd and Ddc. Tatarenkov, A., Sáez, A.G., Ayala, F.J. Gene (1999) [Pubmed]
  19. The genetics of dopa decarboxylase in Drosophila melanogaster. II. Isolation and characterization of dopa-decarboxylase-deficient mutants and their relationship to the alpha-methyl-dopa-hypersensitive mutants. Wright, T.R., Bewley, G.C., Sherald, A.F. Genetics (1976) [Pubmed]
  20. Development of serotonin-containing neurons in Drosophila mutants unable to synthesize serotonin. Vallés, A.M., White, K. J. Neurosci. (1986) [Pubmed]
  21. An analysis of dopa decarboxylase expression during embryogenesis in Drosophila melanogaster. Gietz, R.D., Hodgetts, R.B. Dev. Biol. (1985) [Pubmed]
  22. Genomic organization of the rat aromatic L-amino acid decarboxylase (AADC) locus: partial analysis reveals divergence from the Drosophila dopa decarboxylase (DDC) gene structure. Hahn, S.L., Hahn, M., Joh, T.H. Mamm. Genome (1991) [Pubmed]
  23. Quantitative Trait Loci for Locomotor Behavior in Drosophila melanogaster. Jordan, K.W., Morgan, T.J., Mackay, T.F. Genetics (2006) [Pubmed]
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