Drosophila to Explore Nucleolar Stress.

Area of Science:

• Cell Biology
• Developmental Biology
• Genetics

Background:

• Nucleolar stress arises from impaired ribosome production or function, often leading to ribosomopathies in stem and progenitor cells.
• Drosophila serves as a model organism to study the cellular responses to nucleolar stress, including cell cycle arrest, apoptosis, and autophagy.

Purpose of the Study:

• To investigate the role of nucleolar phosphoprotein of 140 kDa (Nopp140) in nucleolar stress within Drosophila.
• To understand the molecular mechanisms linking nucleolar stress to disease phenotypes, using Drosophila as a model.

Main Methods:

• Depletion of Nopp140, a ribosome biogenesis factor, in Drosophila eye imaginal disc cells and brain neuroblasts.
• Analysis of cellular responses including JNK pathway activation, apoptosis, autophagy, and protein level changes (coilin, Deadpan).
• Observation of cytoplasmic granule formation and assessment of cell proliferation via EdU labeling.

Main Results:

• Nopp140 depletion in eye imaginal discs caused deformities mimicking Treacher Collins syndrome.
• JNK pathway activation was observed in larvae with Nopp140 deletion, inducing pro-apoptotic and autophagy factors.
• Cytoplasmic granules resembling P bodies formed, and coilin levels decreased in most neuroblast types under nucleolar stress, except in resilient Mushroom body neuroblasts.

Conclusions:

• JNK signaling is a central regulator of nucleolar stress responses in Drosophila.
• Nopp140 plays a critical role in maintaining ribosome biogenesis and preventing stress-induced cellular pathologies.
• Specific neuroblast populations, like MB neuroblasts, display resilience to nucleolar stress by maintaining key protein levels.