Discovery of Chinmo, Br-C, and E93 genes sheds light on insect metamorphosis and potential cancer connections

In a recent study published in eLife and conducted by the Institute for Evolutionary Biology (IBE, CSIC-UPF) and the IRB Barcelona, an intriguing discovery has been made regarding the Chinmo gene and its role in initiating the juvenile phase in insects. Additionally, it has been confirmed that the Br-C and E93 genes are involved in regulating insect maturity. Surprisingly, these genes are not only found in insects but are also present in humans, where they act as promoters and suppressors, respectively, of cancer-related processes.

The research, carried out using the fruit fly Drosophila melanogaster and the cockroach Blatella germanica, has shed light on the conservation of these genes throughout the evolutionary history of insects. This finding suggests that they may hold significant significance in the development of metamorphosis, potentially playing a pivotal role in this evolutionary process.

The Chinmo, Br-C, and E93 genes are the hands of the biological clock in insects

Complete metamorphosis in insects, such as flies, involves three distinct developmental stages: embryo formation within the egg, growth through multiple phases as larvae (juvenile stage), and the pupal stage where metamorphosis occurs leading to the formation of the adult organism.

Previous investigations had revealed the significance of the Br-C gene in determining pupal development in insects. In 2019, the same research team from the IBE conducted a study elucidating the vital role of the E93 gene in facilitating complete metamorphosis in insects and initiating the maturation of tissues that eventually form the adult organism. However, until now, the gene responsible for establishing the juvenile stage remained unknown. This recent study has successfully identified the Chimno gene as the primary regulator of this developmental stage in insects.

By selectively removing the Chinmo gene in Drosophila specimens, scientists observed that these insects progressed to the pupal stage without undergoing the complete juvenile stage, prematurely transitioning to adulthood. These findings unequivocally confirm the essential role of Chinmo in juvenile development.

Dr. Xavier Franch, a co-leader of the study and researcher at the IBE (CSIC-UPF), explains, “We have discovered that Chinmo promotes tissue growth during the juvenile stage of Drosophila by maintaining in an undifferentiated state. As long as Chinmo is expressed, cells are unable to differentiate, as the gene inhibits the action of other genes responsible for forming adult tissues.”

Consequently, the study concludes that inactivation of the Chinmo gene is necessary for Drosophila to progress from the juvenile to the pupal stage and successfully undergo metamorphosis. Furthermore, it confirms that the sequential action of three genes—Chinmo, Br-C, and E93—during the larval, pupal, and adult stages, respectively, coordinates the formation of distinct organs that constitute the adult organism.

Growth-regulating genes play a key role in cancerous processes

Chinmo and Br-C, belonging to the extensive family of BTB-ZF transcription factors, are proteins known to be associated with cancer and are also present in humans. While previous research had established Chinmo as a cancer precursor, the roles of Br-C and E93 in this disease remained unknown until now.

Gaining an understanding of the molecular mechanisms governing cell growth can significantly enhance our comprehension of cancer processes. Healthy cells undergo controlled growth, differentiation, and maturation. Conversely, cancer cells experience uncontrolled growth, lack of differentiation, and failure to mature. Therefore, unraveling the roles of Chinmo, Br-C, and E93 could prove crucial for future clinical research, as emphasized by Dr. Jordi Casanova, a co-author of the study and researcher at IRB Barcelona.

The study reveals that Chinmo acts as an oncogenic precursor by promoting tissue growth and inhibiting differentiation, while Br-C and E93 function as tumor suppressors by facilitating tissue maturation.

These findings shed light on the complex molecular dynamics underlying cell growth regulation and provide valuable insights for potential avenues of future research in the field of cancer.

Chinmo reveals how metamorphosis evolved

The process of complete metamorphosis, seen in insects like butterflies and flies, represents an evolutionary innovation that gradually developed from simpler forms of metamorphosis, as observed in cockroaches. To comprehend the gradual progression of this process, researchers investigated the roles of Chinmo, Br-C, and E93 genes in cockroaches.

“By studying the gene functions across different insect species, we gain insights into the workings of . The conservation of Chinmo's function in insects as diverse as flies and cockroaches provides valuable hints about the origins of metamorphosis,” explains Dr. David Martin, a co-leader of the study and researcher at the IBE (CSIC-UPF).

The study's findings suggest that the regulatory actions of Chinmo and E93 in more primitive insects like cockroaches are sufficient to determine the transition from the juvenile to the adult form. However, the introduction of the Br-C gene facilitated the development of pupae and ushered in the concept of complete metamorphosis through the inclusion of a new pupal stage in insects like flies.

Hence, these discoveries shed light on the evolutionary process underlying the transition from simpler metamorphosis to complete metamorphosis, providing crucial insights into the genetic mechanisms responsible for the development of different life stages in diverse insect species.

Source: Institute for Research in Biomedicine (IRB Barcelona)

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