In the movies, spooks and phantoms are often undead humans with unfinished business. But would you be afraid of a ghostly fruit fly?

In 1995, fruit fly researchers Christiane Nüsslein-Volhard and Eric Wieschaus were awarded a Nobel Prize for their research on development. They were interested in understanding how a fertilized egg develops into a complex organism, and were the first to show that development was controlled by genes. In their famous paper published in 1980, they found a small number of genes that were important in determining the body plan and formation of body segments in fruit fly larva.

Four years later, the same researchers published a set of papers on a group of genes that caused developmental defects in fruit fly embryos. When a gene in this group was mutated, the embryos died before the exoskeleton was created. The mutations somehow disrupted the formation of the embryonic cuticle, the protective outer layer that should form around the embryo. The researchers (not without a sense of humor after long grueling hours in the lab) dubbed them the Halloween genes. The genes earned their name not just because they mutated and killed, but because the mutant embryos took on a ghostly appearance. This resulted in gene names such as disembodied, spook, spookier, shadow, shade, shroud, and phantom.

Images of the cuticles of a normal fruit fly embryo and two with mutations in a Halloween gene. Modified from Images of the cuticles of a normal fruit fly embryo and two with mutations in a Halloween gene. Modified from Gilbert, 2004

So what do the Halloween genes do? Since the 1980s, researchers have discovered that all of the Halloween genes are cytochrome P450 (CYP) enzymes involved in synthesizing a steroid hormone called 20-hydroxyecdysone (20E) from cholesterol. 20E is required for metamorphosis and moulting in arthropods such as insects and crabs. As a result, disruption of 20E synthesis in fruit flies blocked formation of the exoskeleton in embryos. Hmm… I had to look all that up.

The Halloween genes encode enzymes that convert cholesterol into the arthropod steroid hormone 20E. Modified from The Halloween genes encode enzymes that convert cholesterol into the arthropod steroid hormone 20E. Modified from Gilbert, 2008

CYP enzymes are found in most species and are involved in a very large variety of processes. In humans, they are involved in regulating hormones (among other things), including steroid hormones (just like in flies!). Steroid hormones are basically a group of steroids that act as hormones in the body, and they are synthesized from cholesterol (just like in flies!). Interestingly, testosterone and anabolic steroids, such as the ones that athletes may take, are actually steroid hormones. Thus, although mammals do not have 20E, they have other steroid hormones are important for development as well as reproduction, metabolism, and homeostasis, which allows cells to adapt to their changing environment. Because of these similarities, research in the Halloween genes may help us better understand how steroid hormones are synthesized in mammals.

Happy Halloween!

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