Key molecular mechanism for tissue regeneration discovered in insects
published on 18/12/2024
A study co-led by the CABD and IRBio (UB) identifies the essential function of a protein control system in the regeneration of tissues and organs 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.
A study co-led by Fernando Casares, from the Centro Andaluz de Biología del Desarrollo (CABD, CSIC-JA-UPO) and Isabel Almudí, from the Institut de Recerca de la Biodiversitat (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 rapid regeneration.
many of its organs. The results, published in the journal Open Biology, open the door to the investigation of this molecular process in the regeneration of organs 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 regenerative capacity compared to other animals. Fernando Casares points out that “understanding how some organisms regenerate their organs efficiently will allow us to understand this process at the molecular, cellular and organ level, and opens a window to understand not only why some organisms regenerate well, but also why we regenerate poorly”.
This work contributes to filling this gap in our knowledge of this process by studying regeneration in the ephemeral Cloeon dipterum, a freshwater insect that only emerges from the water once it reaches adulthood. Thus, aquatic juveniles, also called nymphs, have a pair of gills on each of their first seven abdominal segments. These are flat, paddle-like organs that are essential for respiration, osmoregulation (the maintenance of water and salt balance within the body) and, probably, for the detection of chemicals.
Often, however, these gills are shed from the body to make room for new ones that are generated in a time span of five to nine days. “These new gills not only regenerate, but during the process they grow at a faster rate than during normal development,” says Casares. Experiments carried out by the research team show that this rapid regeneration does not seem to be due to the growth of a specialized region (which is formed in many regeneration processes and is called blastema), but is produced by a uniform increase in cell proliferation throughout the gill.
In this work, in which Carlos A. Martin-Blanco, 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 fundamental for insects to regenerate their appendages. Defective proteins, or those that should be eliminated if they are no longer needed for cell 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 proteasome components 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 related to the overexpression of this molecular process. In fact, there are drugs that block this mechanism and that are used as antitumor drugs.
Isabel Almudí comments that this work brings 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 assays in another insect, the vinegar fly Drosophila, 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 to analyze whether their regenerative capacities are enhanced. This discovery could have implications in fields such as biomedicine, since 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
This press release was written in collaboration with the units of comunication from CSIC, CSIC Andalucía and IRBio (UB).