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Nucleolar stress occurs when ribosome production or function declines. Nucleolar stress in stem cells or progenitor cells often leads to disease states called ribosomopathies. Drosophila offers a robust system to explore how nucleolar stress causes cell cycle arrest, apoptosis, or autophagy depending on the cell type. We provide an overview of nucleolar stress in Drosophila by depleting nucleolar phosphoprotein of 140 kDa (Nopp140), a ribosome biogenesis factor (RBF) in nucleoli and Cajal bodies (CBs). The depletion of Nopp140 in eye imaginal disc cells generates eye deformities reminiscent of craniofacial deformities associated with the Treacher Collins syndrome (TCS), a human ribosomopathy. We show the activation of c-Jun N-terminal Kinase (JNK) in Drosophila larvae homozygous for a Nopp140 gene deletion. JNK is known to induce the expression of the pro-apoptotic Hid protein and autophagy factors Atg1, Atg18.1, and Atg8a; thus, JNK is a central regulator in Drosophila nucleolar stress. Ribosome abundance declines upon Nopp140 loss, but unusual cytoplasmic granules accumulate that resemble Processing (P) bodies based on marker proteins, Decapping Protein 1 (DCP1) and Maternal expression at 31B (Me31B). Wild type brain neuroblasts (NBs) express copious amounts of endogenous coilin, but coilin levels decline upon nucleolar stress in most NB types relative to the Mushroom body (MB) NBs. MB NBs exhibit resilience against nucleolar stress as they maintain normal coilin, Deadpan, and EdU labeling levels.
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Drosophila Retinal Patterning
The Drosophila eye is an outstanding model system for exploring fundamental mechanisms of growth and development. The adult eye is composed of a perfect hexagonal lattice of ∼750 unit eyes, or ommatidia, each containing precisely 20 well-characterized cells. The eye develops from the eye/antennal imaginal disc, a flattened epithelial sac. During larval and pupal development, cells in the disc grow and undergo compartmentalisation, cell cycle arrest, differentiation, directed movement, and apoptosis, all utilising gene networks and signalling pathways similar to those in vertebrates. The genetic accessibility of Drosophila, together with the precision of eye development, makes the fly retina an extremely useful system with which to investigate the roles of genes and signalling pathways in development.
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- Award ID(s):
- 1828327
- PAR ID:
- 10310792
- Date Published:
- Journal Name:
- Encyclopedia of life sciences
- Volume:
- 1
- Issue:
- 4
- ISSN:
- 1476-9506
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/npg.els.0001511
