Chinmo, “the youth gene”

A study conducted by the Institute of Evolutionary Biology (IBE, CSIC-UPF) and the Barcelona Institute of Biomedical Research (IRB Barcelona) and published in the journal eLiferevealed that the Chinmo gene is responsible for establishing the juvenile stage in insects.

The work also confirms that the Br-C and E93 genes play a regulatory role in insect maturity. These genes, which are also present in humans and other mammals, act as promoters and suppressors, respectively, of cancerous processes.

The results of research, carried out with the fruit fly, Drosophila Melanogaster, and the cockroach Blatella germanica, reveal that these genes were conserved throughout the evolution of insects, which is why it is believed that they may have a fundamental role in evolution. of metamorphosis.

Three genes as biological clock hands in insects

Insects that undergo complete metamorphosis, such as flies, go through three stages of development: the embryo, which is generated inside the egg, the larva (juvenile stage) which grows in several stages, and the pupa, stage in which it is produced . metamorphosis to form the adult organism.

Previous studies had found that the Br-C gene determines the formation of pupae in insects. In 2019, the same IBE team that led this study described the essential function of E93 to complete metamorphosis in insects and initiate the maturation of tissues that will form the adult.

However, the gene responsible for determining the juvenile stage was unknown until now. This study identified the Chinmo gene as the main precursor of the juvenile stage in insects.

By deleting the Chinmo gene in Drosophila specimens, it was observed that these insects evolved to the adult stage without completing the juvenile stage.

By deleting the Chinmo gene in Drosophila specimens, the research observed that these insects evolved to the pupal stage without completing the juvenile stage, passing early to the adult stage, confirming that Chinmo is essential for juvenile development.

“We found that Chinmo promotes tissue growth during the juvenile stage of Drosophila by keeping the cells undifferentiated. Thus, while Chinmo is expressed, the cells are unable to differentiate, as it suppresses the action of the genes responsible for the formation of adult tissues”, says Xavier Franch, researcher at IBE (CSIC-UPF) who co-led the study.

In this way, the study concludes that to pass from the juvenile stage to the pupal stage and successfully carry out the metamorphosis, the Chinmo gene has to be inactivated. Likewise, it is confirmed that the sequential action of the three genes: Chinmo, Br-C and E93, during the larval, pupal and adult phases, respectively, coordinate the formation of the different organs that constitute the adult organism.

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A key role in cancer processes

Chinmo and Br-C belong to the large family of BTB-ZF transcription factors, proteins involved in cancer that are also found in humans. Although previous studies have already shown that Chinmo is a precursor of cancer, the role of Br-C and E93 in this disease was unknown until now.

Knowing the molecular workings of cell growth can help better understand cancer processes

Jordi Casanova, IRB researcher

“Knowing the molecular functioning of cell growth can help to better understand cancer processes. Healthy cells grow, differentiate, and mature, cancer cells, on the other hand, grow uncontrollably, fail to differentiate, and fail to mature. For this reason, determining the role of Chinmo, Br-C and E93 could be key for future clinical research”, says Jordi Casanova, IRB researcher and co-author of the study.

Research shows that while Chinmo is an oncogenic precursor, promoting tissue growth and preventing differentiation, C-Br and E93 act as tumor suppressors by activating tissue maturation.

Flies in the pupa stage. / Panagiotis Giannios

Origin of metamorphosis evolution

Complete metamorphosis in insects such as butterflies or flies is an evolutionary innovation that gradually appeared during the evolution of insects that exhibit much simpler metamorphosis, such as cockroaches. To understand how this gradual process occurred, the researchers analyzed the role of Chinmo, Br-C and E93 in cockroaches.

Analyzing the function of these genes in different insect species allows us to observe how evolution works.

David Martín, researcher at IBE

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

In this way, the results of the study indicate that in more basal insects, such as the cockroach, the regulatory action of Chinmo and E93 are sufficient to determine the transition from the juvenile form to the adult form. The introduction of the Br-C gene, however, allowed for the invention of pupae and the appearance of complete metamorphosis through a new pupal stage in insects such as flies.

Reference:

Silvia Chafino et al. “Antagonistic role of BTB-zinc finger chinmo and broad-complex transcription factors in juvenile/pupal transition and growth control” eLife (2023)

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