18-12-2024
Key molecular mechanism for tissue regeneration in insects discovered
Image of a mayfly (Cloeon dipterum) / Isabel Almudí (IRBio)
- A study co-led by the CSIC identifies the essential function of a protein control system in tissue and organ regeneration in a type of insect
- The results contribute to the knowledge of the genetic mechanisms involved in regeneration and provide clues to the role of this molecular process in human diseases
Seville, Wednesday, December 18, 2024
A study co-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 involvement of neddylation, a protein quality control pathway, in tissue regeneration in mayflies (Cloeon dipterum), a type of insect capable of rapidly regenerating many of its organs. The results, published in the journal Open Biology, open the door to research into this molecular process in organ regeneration in vertebrates and in the development of future therapies.
In nature, not all animals have the ability to regenerate damaged or lost organs. In particular, humans have a very limited regeneration capacity compared to other animals. Fernando Casares points out that “understanding how some organisms regenerate their organs effectively will allow us to understand this process at the molecular, cellular and organ level, and opens a window to understanding not only why some organisms regenerate well, but why we regenerate poorly.”
This work contributes to filling this gap in our knowledge about this process by studying regeneration in the mayfly Cloeon dipterum, a freshwater insect that only emerges from the water once it reaches adulthood. 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 respiration, osmoregulation (maintaining water and salt balance within the body) and probably for sensing chemicals.
However, these gills often shed from the body to make way for new ones that are generated within a period of between five and nine days. “These new gills not only regenerate, but during the process they grow at a faster rate than during normal development,” Casares points out. The experiments carried out by the research team show that this rapid regeneration does not seem to be due to the growth of a specialised region (which forms in many regeneration processes and is called the blastema), but is produced by a uniform increase in cell proliferation throughout the gill. In this work, in which Carlos A. Martin-Blanco, a doctoral researcher at the CABD and the University of Barcelona, has played an essential role, a protein quality control pathway called neddylation has been identified as essential for insects to regenerate their appendages. Defective proteins or those that must be eliminated if they are no longer necessary for cellular function are discarded through a specialized machinery called the proteasome. “However, this machinery is subject to regulation and it is precisely the chemical addition of the Nedd8 protein to some of the 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, the functioning of the immune system and tumorigenesis. Curiously, the researchers point out that the development of tumors is related to the overexpression of this molecular process. In fact, there are drugs that block this mechanism and are used as antitumor medicines. Isabel Almudí comments that this work provides new discoveries, but also new questions: “Could it be that organs in the process of regeneration 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 Drosophila vinegar fly, that these mechanisms are conserved within insects, opening doors to investigate whether these processes are also important in organ regeneration in vertebrates.
The next challenge for researchers will be to try to stimulate these processes in organs that regenerate poorly and analyse whether their regenerative capacities increase. This discovery could have implications in fields such as biomedicine, given that regenerative mechanisms in other animals are a source of inspiration for future therapies in humans.
Carlos A. Martín-Blanco, Pablo Navarro, José Esteban-Collado, Florenci Serras, Isabel Almudí and Fernando Casares. Gill regeneration in the mayfly Cloeon uncovers new molecular pathways in insect regeneration. Open Biology. doi.org/10.1098/rsob.240118
Source:
CSIC Communication – Andalusia and Extremadura