Halloween genes

20-hydroxyecdysone, a key regulatory hormone involved in cuticle development in insects

The halloween genes are a set of genes identified in Drosophila melanogaster that influence embryonic development. All of the genes code for cytochrome P450 enzymes in the ecdysteroidogenic pathway (biosynthesis of ecdysone from cholesterol). Ecdysteroids such as 20-hydroxyecdysone and ecdysone influence many of the morphological, physiological, biochemical changes that occur during molting in insects.[1]

Steroid hormones control many aspects of reproduction, development, and homeostasis in higher organisms.[2][3] In arthropods, steroid hormones play equal or even more vital developmental roles, especially in controlling the patterns of gene expression between developmental stages.[1] The forerunner of steroid hormones is cholesterol that vertebrates can synthesize. In contrast, insects need to take up cholesterol in their diet. In 20E biosynthesis, a series of hydroxylation takes place and the genes that encoded the enzymes for catalyzing the hydroxylation were first identified in Drosphilia.[4] Insects have been around since about 500 million years before the first mammal and have continued to be evolutionarily successful. This suggests that exogenous cholesterol was required for the mechanism for steroid hormone biosynthesis.[5]

First elaborated by research groups led by Wieschaus and Nüsslein-Volhard in the early 1980s, the name was coined to collectively name a series of Drosophila embryonic lethal mutations associated with defective exoskeleton formation. Early research showed that when one of the Halloween genes was mutated, fly embryos would die before the exoskeleton was created.[6] Mutants in the halloween gene series include the spook, spookier, phantom (or phm), disembodied (or dib), shadow (or sad), and shade genes.

The mutant homozygous embryos appear phenotypically normal until mid-embryonic development where the embryos exhibit abnormal developmental characters. Some abnormal characteristics include undifferentiated cuticle, a failure of head involution, dorsal closure, compact appearance and abnormal looping of the hindgut. These embryos die before reaching the end of embryogenesis.[5]

The mechanisms of transcriptional regulation of the Halloween genes appear to differ from one another.[7]

  1. ^ a b Gilbert LI, Rybczynski R, Warren JT (2002). "Control and biochemical nature of the ecdysteroidogenic pathway". Annual Review of Entomology. 47: 883–916. doi:10.1146/annurev.ento.47.091201.145302. PMID 11729094.
  2. ^ Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schütz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM (1995). "The nuclear receptor superfamily: the second decade". Cell. 83 (6): 835–39. doi:10.1016/0092-8674(95)90199-X. PMC 6159888. PMID 8521507.
  3. ^ Okamoto, Naoki; Fujinaga, Daiki; Yamanaka, Naoki (2023), "Steroid hormone signaling: What we can learn from insect models", Vitamins and Hormones, 123, Elsevier: 525–554, doi:10.1016/bs.vh.2022.12.006, ISBN 978-0-443-13455-5, PMID 37717997, retrieved 2024-07-29
  4. ^ Rewitz, K.F.; Rybczynski, R.; Warren, J.T.; Gilbert, L.I. (2006-12-01). "The Halloween genes code for cytochrome P450 enzymes mediating synthesis of the insect moulting hormone". Biochemical Society Transactions. 34 (6): 1256–1260. doi:10.1042/BST0341256. ISSN 0300-5127. PMID 17073797.
  5. ^ a b Gilbert, Lawrence I (February 2004). "Halloween genes encode P450 enzymes that mediate steroid hormone biosynthesis in Drosophila melanogaster". Molecular and Cellular Endocrinology. 215 (1–2): 1–10. doi:10.1016/j.mce.2003.11.003. PMID 15026169. S2CID 9215493.
  6. ^ Gilbert LI. (2008). "Drosophila is an inclusive model for human diseases, growth and development". Molecular and Cellular Endocrinology. 293 (1–2): 25–31. doi:10.1016/j.mce.2008.02.009. PMID 18374475. S2CID 27545060.
  7. ^ Kamiyama, Takumi; Niwa, Ryusuke (2022-02-08). "Transcriptional Regulators of Ecdysteroid Biosynthetic Enzymes and Their Roles in Insect Development". Frontiers in Physiology. 13. doi:10.3389/fphys.2022.823418. ISSN 1664-042X. PMC 8863297. PMID 35211033.