Studies in Drosophila have revealed that activin signaling is an important mechanism in intestinal plasticity, influencing the ability of the intestine to contract and expand in response to nutrient availability. This finding has implications for understanding organ adaptation and opens new avenues for exploring colorectal cancer treatments related to disruption of activin signaling.
One of the most striking examples of intestinal plasticity is observed in animals exposed to long periods of fasting, such as hibernating animals or phyton snakes that go months without eating, where the intestine shrinks by as much as 50%. However, it will recover. size after several days of refeeding. Importantly, the ability of the intestine to undergo size changes is widely conserved. Therefore, an increase in intestinal size is observed during pregnancy in humans, which facilitates the uptake of nutrients to support fetal growth.
Drosophila melanogaster is used in the Colombani-Andersen laboratory at the Department of Cell and Neurobiology, Faculty of Biology, University of Copenhagen. Drosophila, to study the mechanisms that regulate intestinal plasticity.The results have just been published in a scientific journal nature communications.
“Taking advantage of Drosophila’s extensive genetic toolbox, we investigated the mechanisms that underpin nutrient-dependent changes in intestinal size,” says Dr. Ditte S. Andersen.
Discovering the mechanism of intestinal size change
This result indicates that nutrient deprivation leads to the accumulation of progenitor cells that cannot differentiate into mature cells, leading to the shrinkage of the intestine. Upon refeeding, these arrested progenitor cells readily differentiate into mature cells and promote intestinal regrowth.
Ditte S. Andersen continued: “We have identified activin as a key regulator of this process. In conditions of nutrient restriction, activin signaling is strongly suppressed, but it is reactivated and responds to refeeding. is required for progenitor cell maturation and intestinal resizing. Activin-dependent intestinal resizing is physiologically important, as inhibition of activin signaling reduces fly survival to intermittent fasting. .”
Regulators of organ plasticity are essential for host adaptation to a constantly changing environment, but the same signals are often deregulated in cancer. Indeed, mutations that affect activin signaling are frequently found in cancer cells from various tissues. Our study provides a starting point to investigate the association between aberrant activin signaling and colorectal cancer development and sets the stage for exploring the efficiency of anti-activin therapeutic strategies in the treatment of colorectal cancer. I’ll arrange it.
Reference: “Drosophila activin adapts gut size to food intake and promotes regenerative growth” by Christian F. Christensen, Quentin Laurisches, Rihab Raudaev, Julian Colombani, and Ditte S. Andersen, 2024 January 4th, nature communications.
DOI: 10.1038/s41467-023-44553-9
