Introducing Chinmo – The Youth Gene

Researchers discover the gene responsible for the juvenile stage in insects; also found in mammals, Chinmo promotes growth and coordinates organ formation.

Insects, with their remarkable ability to undergo complete metamorphosis, have long fascinated scientists seeking to understand the underlying genetic mechanisms governing this transformative process.

Now, a recent study conducted by the Institute for Evolutionary Biology (IBE, CSIC-UPF) and the IRB Barcelona has shed light on the crucial role of three genes – Chinmo, Br-C and E93 – in orchestrating the stages of insect development. Published in eLife, this research provides valuable insights into the evolutionary origins of metamorphosis and sheds new light on the role of these genes in growth, development and cancer regulation [1].

Longevity.Technology: Chinmo might sound like a Pokémon character, but the truth is much more interesting. Conserved throughout the evolution of insects, scientists think it, and the more conventionally-named Br-C and E93, could play a key role in the evolution of metamorphosis, acting as the hands of the biological clock in insects. A maggot is radically different from the fly into which it changes – could understanding and leveraging the biology involved one day allow us to change cultured skin cells into replacement organs or to stop tumors in their early stages of formation? No, Dr Seth Brundle, you can buzz off.

Insects that undergo complete metamorphosis, such as flies, go through the following three stages of development: the embryo, which is formed inside the egg; the larva (juvenile stage), which grows in several phases; and the pupa, which is the stage that encompasses metamorphosis and the formation of the adult organism.

The study focused on two model organisms: the fruit fly Drosophila melanogaster and the cockroach Blattella germanica. Through their investigation, the researchers discovered that the Chinmo gene plays a pivotal role in establishing the juvenile stage of insects, while the Br-C and E93 genes regulate the transition to maturity. These genes are not only present in insects but also found in mammals, including humans, although they have a different function, being involved in the regulation of cancerous processes.

The research team employed a genetic approach, deleting the Chinmo gene in Drosophila specimens and observed that the insects progressed prematurely to the pupal stage, bypassing the juvenile stage. This observation confirms the essential role of Chinmo in juvenile development. Dr Xavier Franch, a co-leader of the study, explains: “We have discovered that Chinmo promotes tissue growth during the juvenile stage of Drosophila by keeping the cells undifferentiated. Thus, while Chinmo is expressed, cells cannot differentiate as the gene suppresses the action of those genes responsible for forming adult tissues [2].”

The study further reveals that the sequential action of Chinmo, Br-C and E93 genes during larval, pupal and adult stages, respectively, coordinates the formation of various organs that shape the adult organism. These findings provide a comprehensive understanding of the genetic regulation underlying insect development and metamorphosis.

Chinmo and Br-C are categorized as BTB-ZF transcription factors, a family of proteins known to be involved in cancer. and that is also found in humans. While Chinmo acts as an oncogenic precursor, promoting tissue growth and hindering differentiation, the part played by Br-C and E93 in cancer development – serving as tumor suppressors by activating tissue maturation – had been previously unknown.

“Understanding the molecular functioning of cell growth can help to better comprehend cancer processes,” explains says Dr Jordi Casanova, an IRB Barcelona researcher and co-author of the study.

“Healthy cells grow, differentiate, and mature. In contrast, cancer cells grow uncontrollably, do not differentiate, and fail to mature. So determining the role of Chinmo, Br-C, and E93 may be key to future clinical research [2].”

The researchers also investigated the function of Chinmo, Br-C and E93 in cockroaches, a species exhibiting a much simpler form of metamorphosis. By comparing their findings across different insect species, the scientists gained insights into the evolutionary progression of metamorphosis.

Introducing Chinmo – The Youth Gene
Flies in pupal stage. Photograph: IRB Barcelona/Panagiotis Giannios

“Analyzing the function of these genes in different species of insects allows us to observe how evolution works,” explains Dr David Martin, a researcher at the IBE (CSIC-UPF) who co-led the study. “The observation that Chinmo function is conserved in insects as evolutionarily separated as flies and cockroaches gives us clues as to how metamorphoses originated.”

The results of the study indicate that the regulatory action of Chinmo and E93 in evolutionarily simpler insects such as the cockroach is sufficient to cause the transition from the juvenile to the adult form. However, when evolution added the Br-C gene into the mix, it allowed the development of the pupae and the appearance of complete metamorphosis through a new pupal stage in insects such as flies.

The fruit fly is often used as a longevity model; by understanding the genetic mechanisms, involved in its metamorphosis, researchers can further explore the fundamental aspects of this extraordinary biological change, as well as gaining valuable insights into cancer regulation. Moreover, these findings provide a platform for further investigations into the evolutionary origins of metamorphosis and its subsequent impact on species diversification and how we might be able to use the pathways involved to regulate growth, repair and rejuvenation – perhaps effecting our own extraordinary changes on our lifespan and healthspan.

[1] https://elifesciences.org/articles/84648
[2] https://www.irbbarcelona.org/en/news/scientific/chinmo-youth-gene

Photographs: IRB Barcelona/Panagiotis Giannios. Main image shows the adult wing precursor imaginal cells of Drosophila melanogaster [Panagiotis Giannios].