Tissue regeneration in insects is no longer a ‘mystery’

A group of scientists has discovered a molecular mechanism present in the tissue of the insects which is essential for tissue regeneration and that could be possible provide new clues about how proteins work intervene in the process.

A study led by Fernando Casares, from the Andalusian Center for Developmental Biology (CABD, CSIC-JA-UPO) and Isabel Almudí, from the Biodiversity Research Institute (IRBio) of the University of Barcelona, ​​shows the implications of neddylation, a pathway for protein quality control in tissue regeneration in mayflies (Cloeon dipterum), a species of insect that is able to rapidly regenerate many of its organs regenerate. The results, published in the journal Open Biology, open the door to research into this molecular process organ regeneration in vertebrates and in the development of future therapies.

Research into regeneration in insects

In nature, not all animals have the ability to regenerate damaged or lost organs. In particular, humans have a very limited capacity for regeneration compared to other animals. Fernando Casares points out that “understanding how some organisms regenerate their organs efficiently It will allow us to understand this process at the molecular, cellular and organ levels, opening a window for us to understand not only why some organisms regenerate well, but also why we regenerate poorly.”

This job contributes to filling this empty space in our knowledge about this process by studying regeneration in the mayfly Cloeon dipterum, a freshwater insect that only emerges from the water when it is an adult. For this reason, aquatic juveniles, also called nymphs, have a pair of gills in each of their first seven abdominal segments. These are flat, paddle-like organs that are essential for breathing, osmoregulation (maintaining water and salt balance in the body), and probably for sensing chemicals.

However, these gills often detach from the body to make room for new ones that are generated within a period of five to nine days. “These new gills not only regenerate, but in the process they grow faster than during normal development,” Casares points out. This is evident from the research team’s experiments This rapid regeneration does not appear to be the result of growth of a specialized area (which is formed in many regeneration processes and called blastema), but is produced by a uniform increase in cell proliferation throughout the gill.

The function of proteins

In this work, in which Carlos A. Martin-Blanco, PhD candidate at the CABD and the University of Barcelona, ​​​​has played an essential role, a way of quality control of proteins, called neddylation, as fundamental so that insects can regenerate their appendages.

Las defective proteins or proteins that need to be removed When they are no longer needed for cellular function, they are discarded via specialized machinery called a proteasome. “However, this machinery is subject to regulation and it is precisely the chemical addition of the Nedd8 protein to some components of the proteasome that activates this machinery,” explains Martín-Blanco.

In addition to its role in regeneration, neddylation is involved in the regulation of metabolism, immune system function and tumorigenesis. Interestingly, the researchers point out that tumor development is linked to the overexpression of this molecular process. There are even drugs that block this mechanism and are used as anti-tumor drugs. Isabel Almudí notes this This work produces new discoveriesbut also new questions: “Could it be that regenerating organs and tumors share some molecular mechanisms?”

A door to future research

The published work identifies other mechanisms involved in regeneration, such as those related to the activin organ growth control pathway, or the Lin28 protein, which regulates the stability of certain RNAs. It also shows, through functional tests in another insect, the vinegar fly Drosophila, that these mechanisms are conserved in insects, opening doors to investigate whether these processes are also important. in organ regeneration in vertebrates.

The next challenge for researchers will be to stimulate these processes in organs that regenerate poorly and analyze whether their regenerative capacities increase. This discovery could have many implications in other areas, such as biomedicineas the regenerative mechanisms used by other animals provide a source of inspiration that could be applied to future therapies in humans.