Summary: Researchers resolved a 112-year-old genetic mystery, while mapping a critical gut-brain signaling loop that dictates early-life survival. The study investigated the post-hatching behavioral timeline of the fruit fly Drosophila melanogaster.
The team discovered that neonatal flies must execute a strict procedural sequence: they must first expel their primitive metabolic waste, known as meconium, before the brain can safely activate independent feeding drives. By examining a historic genetic mutation discovered in 1914, the team isolated a severe developmental defect that creates a physical hindgut plug, coined “Reinger’s knot”, proving that mechanical intestinal obstruction directly overrides the brain, inducing severe food avoidance, profound lethargy, and protective hypersomnia (excessive sleep).
Key Facts
- The 112-Year-Old Mutation Unlocked: In 1914, early geneticists discovered that fruit flies with a mutated apterous gene failed to develop wings and died prematurely. For over a century, the exact biological cause of this rapid early mortality remained entirely unknown. The Kempf Lab has officially revealed that apterous is a master regulator of hindgut architecture, and its absence causes fatal gastrointestinal failure.
- The Post-Hatching Survival Sequence: In healthy organisms, the first hours of life demand precise coordination. The gut must first complete meconium elimination before the central nervous system triggers the appetite drive to begin independent feeding.
- Discovery of “Reinger’s Knot”: First author Cindy Reinger identified the physical cause of the lethal blockage. Healthy flies develop four highly specialized rectal papillae designed to reabsorb water and balance internal fluids. In apterous mutants, these structures fail to form, fusing instead into a solid, plug-like tissue mass in the hindgut that completely seals the digestive tract.
- Intestinal Obstruction Silences Hunger: Despite experiencing severe systemic starvation, flies suffering from this intestinal blockage completely avoid food. The mechanical fullness and pressure signals of the blocked gut directly override the brain’s baseline hunger pathways.
- Hypersomnia as a Survival Handbrake: Blocked flies exhibit profound lethargy and sleep for unusually long intervals. Neuroscientists hypothesize this hypersomnia serves as a metabolic handbrake, allowing the organism to conserve its limited internal energy reserves to prolong survival.
- Proboscis Rhythmic Motility Loops: While locked in this deep, prolonged sleep state, the mutant flies rhythmically move their mouthparts (proboscis). This behavior appears to be an involuntary, evolutionary reflex designed to stimulate gastrointestinal motility in a mechanical effort to clear the intestinal plug.
- Direct Evolutionary Parallels to Human Pathology: The symptoms captured in these fruit fly models mirror human intestinal obstructions, such as Hirschsprung’s disease or meconium ileus in newborns. These conditions trigger severe constipation, loss of appetite, systemic lethargy, intestinal swelling, and fatal tissue rupture, proving that Drosophila is a powerful, high-velocity model to map human enteric-nervous-system disorders.
Source: University of Basel
The first hours of life are critical for the survival and thriving of animals. Two key steps occur during this time: the excretion of metabolic waste – known as meconium – and the beginning of independent feeding.
Until recently, it was unclear how these two processes are connected and how the gut might influence eating and sleeping behavior. Understanding these links is of broad interest and also intensively investigated in humans because gut-brain communication is increasingly implicated in human health and disease.
The fruit fly Drosophila melanogaster faces the same challenge after hatching. Prof. Anissa Kempf’s team at the Biozentrum, University of Basel, found that timing matters. They discovered that young flies only start feeding after partial meconium elimination. However, flies suffering from intestinal obstruction avoid food, sleep unusually long, and die prematurely. These findings suggest that gut function directly affects eating and sleeping behavior.
Genetic defect causes intestinal blockage
The gut problem can be traced back to a gene that plays an important role in fruit fly development. As early as 1914, scientists discovered that flies with a defect in the apterous gene fail to develop wings. They also noticed back then that these flies die young.
“We have now identified the cause of early death and resolved a question that has puzzled researchers for more than a century,” says Kempf. “The gene defect not only affects wing development but also proper hindgut development, leading to intestinal blockage.”
Intestinal blockage makes flies lethargic
Due to the blockage, the flies cannot expel their meconium after hatching. Over time, they become increasingly lethargic and sleepy, and they don’t feed even though they are hungry.
“We think that the flies sleep more in order to conserve energy and thus survive longer,” explains Cindy Reinger, first author of the study. “While sleeping, flies also move their proboscis rhythmically, which may help stimulate gut motility. Perhaps this is a desperate attempt to get rid of the meconium.”
The researchers also discovered the cause of the fatal intestinal blockage. “In healthy flies, four so-called rectal papillae form during early development. These structures are essential for water reabsorption to minimize water loss,” says Reinger. “Instead of developing four normal papillae, the mutant flies form a plug-like structure in the hindgut that completely blocks the intestine. We named it the Reinger’s knot.”
Parallels with humans
The study clearly demonstrates that gut function is linked to feeding, sleep and ultimately survival. The research also brings up new questions: How does the gut communicate with the brain? How does the intestine regulate sleep? And how does the body know when to start eating?
Many of the symptoms seen in fruit flies resemble intestinal obstruction in humans, including constipation, loss of appetite, lethargy, swelling of the gut, and tissue damage that can lead to intestinal rupture. The study suggests that gut signals may trigger some of these symptoms.
Because fruit flies share many biological processes with humans, they provide a powerful model for investigating the mechanisms behind digestive disorders and gut-brain communication.
Key Questions Answered:
A: It is an evolutionary survival mechanism to protect the body’s energy. When the gut is completely blocked by “Reinger’s knot,” the fly cannot pass waste or digest new food. The gut sends urgent stress signals to the brain, which triggers deep, prolonged sleep. This hypersomnia acts like a metabolic handbrake, lowering the fly’s energy expenditure so it can stay alive longer while its body desperately tries to clear the blockage.
A: Because fruit flies and humans share a vast majority of the same basic biological processes, cell-signaling pathways, and genetic blueprints. The ways a fruit fly’s gut communicates with its brain to control hunger and rest are fundamentally similar to the human enteric nervous system. Using fruit flies allows neuroscientists to rapidly map out the exact genes and neural circuits that go wrong during severe digestive illnesses.
A: It proves that gastrointestinal fullness and clearance are direct regulators of behavioral drives in the brain. This enteroneurological checkpoint ensures an animal does not ingest new food when its digestive tract is already full of embryonic waste. Understanding this feedback loop helps doctors better comprehend why human infants with serious intestinal blockages experience a complete loss of appetite, profound lethargy, and systemic body shut-down.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuroscience and sleep research news
Author: Angelika Jacobs
Source: University of Basel
Contact: Angelika Jacobs – University of Basel
Image: The image is credited to Biozentrum, University of Basel
Original Research: Open access.
“Intestinal obstruction impairs feeding and promotes sleep in Drosophila melanogaster” by Cindy Reinger, Laura Blackie, Alexandra M. Medeiros, Hugo Gillet, Carolin Kring, Pedro Gaspar, Dafni Hadjieconomou, Michèle Sickmann, Markus Affolter, Irene Miguel-Aliaga, Martin Müller, and Anissa Kempf. Science Advances
DOI:10.1126/sciadv.ady2183
Abstract
Intestinal obstruction impairs feeding and promotes sleep in Drosophila melanogaster
At the onset of life, feeding must be initiated while developmental waste products—the meconium—need to be eliminated. Although these two fundamental physiological processes are interconnected, their mechanistic coupling remains poorly understood.
Using Drosophila as a model system, we investigated the coordination of these processes. We show that meconium excretion starts shortly after eclosion and that feeding initiation begins only after partial meconium elimination. We identified a cis-regulatory element associated with the apterous gene that is required for proper hindgut development. Its disruption prevents meconium excretion and leads to intestinal obstruction.
As a result, flies with a defective element avoid food and exhibit increased proboscis extension sleep. Experimental inhibition of excretion in freshly eclosed flies recapitulates these phenotypes, indicating that intestinal blockage is sufficient to impair feeding and alter sleep/wake states.
The progression of phenotypes parallels hallmarks of mechanical gut obstruction in humans, suggesting that the observed effects may arise from broader physiological consequences of intestinal blockage.
Our findings uncover a link between intestinal clearance, feeding, sleep, and survival, with potential implications for understanding similar processes across species.
