20-hydroxyecdysone, a key regulatory hormone involved in cuticle development in insectsThe halloween genes are a set of

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

s identified in ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...

'' that influence embryonic development. All of the genes code for cytochrome P₄₅₀ enzymes in the ecdysteroidogenic pathway (biosynthesis of

ecdysone Ecdysone is a prohormone of the major insect molting hormone 20-hydroxyecdysone, which is secreted from the prothoracic glands. It is of steroidal structure. Insect molting hormones (ecdysone and its homologues) are generally called ecdysteroids. ...

from

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

). Ecdysteroids such as

20-hydroxyecdysone 20-Hydroxyecdysone (ecdysterone or 20E) is a naturally occurring ecdysteroid hormone which controls the ecdysis (moulting) and metamorphosis of arthropods. It is therefore one of the most common moulting hormones in insects, crabs, etc. It is als ...

and

influence many of the morphological, physiological, biochemical changes that occur during molting in insects. Steroid hormones control many aspects of reproduction, development, and

homeostasis In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...

in higher organisms. In arthropods, steroid hormones play equal or even more vital developmental roles, especially in controlling the patterns of gene expression between developmental stages. 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''. 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. 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 An exoskeleton (from Greek ''éxō'' "outer" and ''skeletós'' "skeleton") is an external skeleton that supports and protects an animal's body, in contrast to an internal skeleton (endoskeleton) in for example, a human. In usage, some of the ...

formation. Early research showed that when one of the Halloween genes was mutated, fly embryos would die before the exoskeleton was created. 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.

Descriptions

The ''spook'' gene (Cyp307a1) is expressed in the

prothoracic gland The prothoracic glands are either of a pair of endocrine glands located in the prothorax of certain insects that regulate molting. They have an ectodermal origin and secrete ecdysteroids, such as ecdysone and 20-hydroxyecdysone 20-Hydroxyecdyson ...

, and in conjunction with the gene product of ''spookier'' (Cyp307a2), converts 7-dehydrocholesterol to Δ⁴-diketol. The ''phantom'' gene (Cyp306a1) encodes an encoding the

microsomal In cell biology, microsomes are heterogeneous vesicle-like artifacts (~20-200 nm diameter) re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, liv ...

25-hydroxylase. Strong

expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...

of ''phm'' is restricted to the prothoracic gland cells of the ''Drosophila'' larval ring gland. The gene product converts 2,22,25dE-ketodiol to 2,22dE-ketotriol. The ''disembodied'' gene (Cyp302a1) codes for a cytochrome P₄₅₀ enzyme that adds a

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydro ...

group to the carbon-22 position of 2,22,dE-ketotriol to make 2-deoxyecdysone. ''dib'' mutants are defective in producing their cuticle and have severe defects in morphological processes such as head involution, dorsal closure and gut development. The ''shadow'' gene (Cyp315a1) product produces ecdysone from 2-deoxyecdysone. The ''shade'' gene (Cyp314a1) codes for an Ecdysone 20-monooxygenase responsible for adding a hydroxyl group to the 20C-position of ecdysone to make 20-hydroxyecdysone, the final step in the biosynthetic pathway.

References

{{Cytochrome P450 Developmental genes and proteins Drosophila melanogaster genes