Gene Symbol: sad
Description: shadow
Alias: 315a1, CG14728, CYP315A1, Cyp315a1, Dmel\CG14728, Sad, shadow, CG14728-PA, cytochrome P450, ecdysteroid hydroxylase, karmoisin ghost, sad-PA
Species: fruit fly
Products:     sad

Top Publications

  1. Warren J, Petryk A, Marques G, Jarcho M, Parvy J, Dauphin Villemant C, et al. Molecular and biochemical characterization of two P450 enzymes in the ecdysteroidogenic pathway of Drosophila melanogaster. Proc Natl Acad Sci U S A. 2002;99:11043-8 pubmed
    Five different enzymatic activities, catalyzed by both microsomal and mitochondrial cytochrome P450 monooxygenases (CYPs), are strongly implicated in the biosynthesis of ecdysone (E) from cholesterol...
  2. Parvy J, Blais C, Bernard F, Warren J, Petryk A, Gilbert L, et al. A role for betaFTZ-F1 in regulating ecdysteroid titers during post-embryonic development in Drosophila melanogaster. Dev Biol. 2005;282:84-94 pubmed
    ..The recent identification of genes coding for cytochrome P450 enzymes involved in Drosophila ecdysteroidogenesis provides new molecular tools to investigate the regulation ..
  3. Ono H, Rewitz K, Shinoda T, Itoyama K, Petryk A, Rybczynski R, et al. Spook and Spookier code for stage-specific components of the ecdysone biosynthetic pathway in Diptera. Dev Biol. 2006;298:555-70 pubmed
    ..genes, that are required for embryonic viability and cuticle deposition, have been shown to code for several cytochrome P450 enzymes that catalyze the terminal hydroxylation steps in the conversion of cholesterol to the molting ..
  4. Hackney J, Zolali Meybodi O, Cherbas P. Tissue damage disrupts developmental progression and ecdysteroid biosynthesis in Drosophila. PLoS ONE. 2012;7:e49105 pubmed publisher
    ..Finally, we show that developmental delays induced by tissue damage are associated with decreased expression of genes involved in ecdysteroid synthesis and signaling. ..
  5. Petryk A, Warren J, Marques G, Jarcho M, Gilbert L, Kahler J, et al. Shade is the Drosophila P450 enzyme that mediates the hydroxylation of ecdysone to the steroid insect molting hormone 20-hydroxyecdysone. Proc Natl Acad Sci U S A. 2003;100:13773-8 pubmed
    ..We show here that the Drosophila E-20-monooxygenase (E20MO) is the product of the shade (shd) locus (cytochrome p450, CYP314a1)...
  6. Moeller M, Danielsen E, Herder R, O Connor M, Rewitz K. Dynamic feedback circuits function as a switch for shaping a maturation-inducing steroid pulse in Drosophila. Development. 2013;140:4730-9 pubmed publisher
    ..Activation of this switch-like mechanism ensures a rapid, self-limiting PG response that functions in producing steroid oscillations that can guide the decision to terminate growth and promote maturation. ..
  7. Giesen K, Lammel U, Langehans D, Krukkert K, Bunse I, Klämbt C. Regulation of glial cell number and differentiation by ecdysone and Fos signaling. Mech Dev. 2003;120:401-13 pubmed
    ..In a genetic screen we have identified mutations in disembodied, rippchen, spook, shade, shadow, shroud and tramtrack that all share a number of phenotypic traits, including defects in cuticle differentiation ..
  8. Warren J, Petryk A, Marqu s G, Parvy J, Shinoda T, Itoyama K, et al. Phantom encodes the 25-hydroxylase of Drosophila melanogaster and Bombyx mori: a P450 enzyme critical in ecdysone biosynthesis. Insect Biochem Mol Biol. 2004;34:991-1010 pubmed publisher
    We have reported recently the identification and characterization of the last three mitochondrial cytochrome P450 enzymes (CYP) controlling the biosynthesis of 20-hydroxyecdysone, the molting hormone of insects...
  9. Neubueser D, Warren J, Gilbert L, Cohen S. molting defective is required for ecdysone biosynthesis. Dev Biol. 2005;280:362-72 pubmed
    ..Here, we report identification of one such gene, which we call molting defective, on the basis of its lethal phenotype. molting defective encodes a nuclear zinc finger protein required for ecdysone biosynthesis. ..

More Information


  1. McBrayer Z, Ono H, Shimell M, Parvy J, Beckstead R, Warren J, et al. Prothoracicotropic hormone regulates developmental timing and body size in Drosophila. Dev Cell. 2007;13:857-71 pubmed
    ..These results indicate that final body size in insects is determined by a balance between growth-rate regulators such as insulin and developmental timing cues such as PTTH that set the duration of the feeding interval. ..
  2. Xiang Y, Liu Z, Huang X. br regulates the expression of the ecdysone biosynthesis gene npc1. Dev Biol. 2010;344:800-8 pubmed publisher
    ..These results imply that ecdysone could potentially act through its early response gene br to achieve positive feedback regulation of ecdysone biosynthesis during development. ..
  3. Gibbens Y, Warren J, Gilbert L, O Connor M. Neuroendocrine regulation of Drosophila metamorphosis requires TGFbeta/Activin signaling. Development. 2011;138:2693-703 pubmed publisher
    ..As steroid hormone production in C. elegans and mammals is also influenced by TGF?/Activin signaling, this family of secreted factors may play a general role in regulating developmental transitions across phyla...
  4. Ameku T, Niwa R. Mating-Induced Increase in Germline Stem Cells via the Neuroendocrine System in Female Drosophila. PLoS Genet. 2016;12:e1006123 pubmed publisher
    ..Our study illustrates how female GSC activity is coordinately regulated by the neuroendocrine system to sustain reproductive success in response to mating. ..
  5. Vamos E, Boros I. The C-terminal domains of ADA2 proteins determine selective incorporation into GCN5-containing complexes that target histone H3 or H4 for acetylation. FEBS Lett. 2012;586:3279-86 pubmed publisher
    ..Our findings demonstrate that the ADA2 C-terminal regions play an important role in the specific incorporation of ADA2 into SAGA- or ATAC-type complexes, which in turn determines H3- or H4-specific histone targeting. ..
  6. Pankotai T, Popescu C, Martin D, Grau B, Zsindely N, Bodai L, et al. Genes of the ecdysone biosynthesis pathway are regulated by the dATAC histone acetyltransferase complex in Drosophila. Mol Cell Biol. 2010;30:4254-66 pubmed publisher
    ..The cytochrome genes (spookier, phantom, disembodied, and shadow) involved in steroid conversion in the ring gland are downregulated, while the gene shade, which is involved in ..
  7. Vandersmissen H, Van Hiel M, Van Loy T, Vleugels R, Vanden Broeck J. Silencing D. melanogaster lgr1 impairs transition from larval to pupal stage. Gen Comp Endocrinol. 2014;209:135-47 pubmed publisher
    ..was a reduced ecdysteroid titer, which is in line with significantly reduced transcript levels detected for the Halloween genes shadow (sad) and spookier (spok) in the third instar lgr1 RNAi larvae compared to the control condition.
  8. Danielsen E, Moeller M, Dorry E, Komura Kawa T, Fujimoto Y, Troelsen J, et al. Transcriptional control of steroid biosynthesis genes in the Drosophila prothoracic gland by ventral veins lacking and knirps. PLoS Genet. 2014;10:e1004343 pubmed publisher
  9. Chen S, Li X. Transposable elements are enriched within or in close proximity to xenobiotic-metabolizing cytochrome P450 genes. BMC Evol Biol. 2007;7:46 pubmed
    ..genes, we scanned two alleles per each of the six xenobiotic-metabolizing Helicoverpa zea cytochrome P450 loci, including CYP6B8, CYP6B27, CYP321A1, CYP321A2, CYP9A12v3 and CYP9A14, for the presence of transposon ..
  10. Shaik K, Meyer F, Vázquez A, Flötenmeyer M, Cerdán M, Moussian B. δ-Aminolevulinate synthase is required for apical transcellular barrier formation in the skin of the Drosophila larva. Eur J Cell Biol. 2012;91:204-15 pubmed publisher
    ..We conclude that at least two modules--an apical protein-chitin lattice and the lateral septate junctions, act in parallel to ensure Drosophila skin impermeability. ..
  11. Chavoshi T, Moussian B, Uv A. Tissue-autonomous EcR functions are required for concurrent organ morphogenesis in the Drosophila embryo. Mech Dev. 2010;127:308-19 pubmed publisher
    ..The results suggest that mid-embryonic EcR-activation imparts a level of gene regulation during embryonic organogenesis that has been largely overlooked, and possibly facilitates synchronized development of individual organs. ..
  12. Pahi Z, Kiss Z, Komonyi O, Borsos B, Tora L, Boros I, et al. dTAF10- and dTAF10b-Containing Complexes Are Required for Ecdysone-Driven Larval-Pupal Morphogenesis in Drosophila melanogaster. PLoS ONE. 2015;10:e0142226 pubmed publisher
    ..We propose that distinct forms of dTFIID and/or dSAGA exist during Drosophila metamorphosis, wherein different TAF compositions serve to target RNAPII at different developmental stages and tissues. ..
  13. Williams S, Dew Budd K, Davis K, Anderson J, Bishop R, Freeman K, et al. Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila. G3 (Bethesda). 2015;5:2817-29 pubmed publisher
  14. Niwa Y, Niwa R. Neural control of steroid hormone biosynthesis during development in the fruit fly Drosophila melanogaster. Genes Genet Syst. 2014;89:27-34 pubmed
    ..The implications from studies with other insects are also discussed. ..
  15. Huang X, Warren J, Gilbert L. New players in the regulation of ecdysone biosynthesis. J Genet Genomics. 2008;35:1-10 pubmed publisher
    ..Here we summarized recent findings in the regulation of ecdysone biosynthesis from the aspects of cell signaling, key biosynthetic enzymes and substrate cholesterol trafficking. ..
  16. Talamillo A, Sánchez J, Cantera R, Pérez C, Martin D, Caminero E, et al. Smt3 is required for Drosophila melanogaster metamorphosis. Development. 2008;135:1659-68 pubmed publisher
    ..In summary, our study indicates that Smt3 is required for the ecdysteroid synthesis pathway at the time of puparium formation. ..
  17. Park J, Choi Y, Thao D, Kim Y, Yamaguchi M, Yoo M. DREF is involved in the steroidogenesis via regulation of shadow gene. Am J Cancer Res. 2012;2:714-25 pubmed
    ..We found a DRE-like sequence (-625 to -632) in the 5'-flanking region of the Drosophila shadow gene, which catalyzes the conversion of 2-deoxyecdysone to ecdysone, and demonstrated that shadow is a novel ..
  18. Neuman S, Ihry R, Gruetzmacher K, Bashirullah A. INO80-dependent regression of ecdysone-induced transcriptional responses regulates developmental timing in Drosophila. Dev Biol. 2014;387:229-39 pubmed publisher
  19. Belles X, Piulachs M. Ecdysone signalling and ovarian development in insects: from stem cells to ovarian follicle formation. Biochim Biophys Acta. 2015;1849:181-6 pubmed publisher
    ..This article is part of a Special Issue entitled: Nuclear receptors in animal development. ..
  20. Rewitz K, O Connor M, Gilbert L. Molecular evolution of the insect Halloween family of cytochrome P450s: phylogeny, gene organization and functional conservation. Insect Biochem Mol Biol. 2007;37:741-53 pubmed
    ..During evolution selective forces have preserved the Halloween genes encoding cytochrome P450 (P450) enzymes that mediate the biosynthesis of 20E...
  21. Llorens J, Metzendorf C, Missirlis F, Lind M. Mitochondrial iron supply is required for the developmental pulse of ecdysone biosynthesis that initiates metamorphosis in Drosophila melanogaster. J Biol Inorg Chem. 2015;20:1229-38 pubmed publisher
    ..Furthermore, mitochondrial iron is also essential for normal larval growth. ..
  22. Mieszczanek J, de la Roche M, Bienz M. A role of Pygopus as an anti-repressor in facilitating Wnt-dependent transcription. Proc Natl Acad Sci U S A. 2008;105:19324-9 pubmed publisher
    ..This indicates an anti-repressor function of Pygo: we propose that Pygo predisposes Drosophila TCF target genes for rapid Wingless-induced transcription, or that it protects them against premature shut-down. ..
  23. Valzania L, Ono H, Ignesti M, Cavaliere V, Bernardi F, Gamberi C, et al. Drosophila 4EHP is essential for the larval-pupal transition and required in the prothoracic gland for ecdysone biosynthesis. Dev Biol. 2016;410:14-23 pubmed publisher
    ..Taken together, these results uncover a novel essential function for 4EHP in regulating ecdysone biosynthesis. ..
  24. Tonning A, Helms S, Schwarz H, Uv A, Moussian B. Hormonal regulation of mummy is needed for apical extracellular matrix formation and epithelial morphogenesis in Drosophila. Development. 2006;133:331-41 pubmed
  25. Komura Kawa T, Hirota K, Shimada Niwa Y, Yamauchi R, Shimell M, Shinoda T, et al. The Drosophila Zinc Finger Transcription Factor Ouija Board Controls Ecdysteroid Biosynthesis through Specific Regulation of spookier. PLoS Genet. 2015;11:e1005712 pubmed publisher
    ..These observations imply that the main biological function of Ouib is to specifically regulate spookier transcription during Drosophila development. ..
  26. Mansilla A, Martín F, Martín D, Ferrús A. Ligand-independent requirements of steroid receptors EcR and USP for cell survival. Cell Death Differ. 2016;23:405-16 pubmed publisher
    ..These novel and context-dependent functional properties for EcR and USP receptors may help to understand the heterogeneous responses to steroid-based therapies in human pathologies. ..
  27. Wright A, Fox A, Johnson K, Zinn K. Systematic screening of Drosophila deficiency mutations for embryonic phenotypes and orphan receptor ligands. PLoS ONE. 2010;5:e12288 pubmed publisher
    ..In the future, these deficiency kits will allow Drosophila researchers to rapidly and efficiently execute genome-wide anatomical screens that require examination of individual embryos at high magnification. ..
  28. Fresán U, Cuartero S, O Connor M, Espinàs M. The insulator protein CTCF regulates Drosophila steroidogenesis. Biol Open. 2015;4:852-7 pubmed publisher the prothoracic gland is required for full transcriptional activation of the Halloween genes spookier, shadow and noppera-bo, which encode ecdysone biosynthetic enzymes, and for proper timing of ecdysone-responsive gene ..
  29. Kasai S, Tomita T. Male specific expression of a cytochrome P450 (Cyp312a1) in Drosophila melanogaster. Biochem Biophys Res Commun. 2003;300:894-900 pubmed
    Using cDNA array techniques, the transcriptional levels of Drosophila cytochrome P450 (P450) genes were compared between male and female flies...
  30. Ranson H, Claudianos C, Ortelli F, Abgrall C, Hemingway J, Sharakhova M, et al. Evolution of supergene families associated with insecticide resistance. Science. 2002;298:179-81 pubmed
    ..The analyses also provide the means for identifying previously unknown molecules involved in fundamental biological processes such as development. ..