Nuclear pore complexes (NPCs), composed of nucleoporins (Nups), affect nucleocytoplasmic transport, thus influencing cell division and gene regulation. Nup107 subcomplex members have been studied in housekeeping functions, diseases, and developmental disorders. We report a unique regulatory function for Nup107 in metamorphic transition during Drosophila development. RNA interference (RNAi)-mediated Nup107-depleted larvae were arrested in the third-instar larval stage with no signs of pupariation. This lack of pupariation is primarily due to inhibited nuclear translocation and transcriptional activation by EcR. We demonstrate the involvement of Nup107 in the transcription of the Halloween genes, modulating ecdysone biosynthesis and the EcR pathway activation. The regulation of EcR-mediated metamorphosis by the receptor tyrosine kinase, torso, is well documented. Accordingly, overexpression of the torso and MAP-kinase pathway activator, rasV12, in the Nup107 depletion background rescues the phenotypes, implying that Nup107 is an epistatic regulator of Torso-mediated activation of EcR signaling during metamorphosis.
Keywords: D. melanogaster; Halloween genes; Nup107; Torso; developmental biology; ecdysone; genetics; genomics; metamorphosis; nucleoporins.
Fruit flies are a widely used model organism for genetic and developmental studies because of their genetic similarity to humans. One example is the study of metamorphosis, the process during which flies develop from eggs into larvae, pupae, and ultimately adults. A comparable process in mammals is puberty, when juveniles mature into fully developed adults. Puberty involves profound physical changes, such as the attainment of sexual maturity and the emergence of new social behaviors. These major life transitions are primarily regulated by hormonal signals from the brain, ovaries and adrenal glands. Imbalances in these hormones can delay or disrupt pubertal development. However, the underlying mechanisms remain incompletely understood. To address this gap, Kawadkar et al. used established genetic tools to reduce or eliminate the nuclear pore complex protein Nup107 in fruit flies. This protein is essential for the movement of molecules between the nucleus and the surrounding space, the cytoplasm. Reduced levels of Nup107 decreased ecdysone production, the steroid hormone needed to start metamorphosis. As a result, the development of fruit fly larvae was disrupted, with animals failing to progress efficiently to the pupal stage. Kawadkar et al. further showed that the ecdysone receptor did not properly move into the nucleus, where it would activate specific genes necessary for metamorphosis. This prevented gene expression essential for developmental progression. The findings of Kawadkar et al. suggest that Nup107 may have a broader role in developmental processes that depend on steroid hormones. Indeed, in humans, Nup107 mutations are known to disrupt gonad development. In insects, the production of ecdysone is indirectly affected by Nup107. Supporting this, feeding synthetic ecdysone to Nup107-depleted larvae partially restored metamorphosis, allowing the animals to reach the pupal stage. Similarly, overexpressing the torso gene, which is part of the signalling pathway that stimulates ecdysone production, fully rescued timely metamorphosis, suggesting that activating the hormone pathway can compensate for the defects caused by reduced Nup107 levels. Overall, these results clarify how Nup107 controls the production of the steroid hormone ecdysone at the start of metamorphosis in fruit flies. This work opens new avenues for investigating whether Nup107 performs similar roles during steroid hormone-dependent puberty in humans. Furthermore, these findings suggest that Nup107 may regulate broader neuroendocrine functions in the brain, with wide-ranging implications for the development of an organism.
© 2025, Kawadkar et al.