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Published on: July 25, 2017
Yorkie ensures robust tissue growth in Drosophila ribosomal protein mutants
Yayoi Wada1, Shizue Ohsawa2, Tatsushi Igaki1
1Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyoku, Kyoto 607-8501, Japan.
Abstract:
Heterozygosity of ribosomal protein genes causes a variety of developmental abnormalities in humans, which are collectively known as ribosomopathies, yet the underlying mechanisms remain elusive. Here, we analyzed Drosophila Minute (M)/+ mutants, a group of mutants heterozygous for ribosomal protein genes that exhibit a characteristic thin-bristle phenotype. We found that, although M/+ flies develop essentially normal wings, simultaneous deletion of one copy of the Hippo pathway effector yki resulted in severe wing growth defects. These defects were caused by JNK-mediated cell death in the wing pouch via Eiger/TNF signaling. The JNK activation in M/+, yki/+ wing discs required the caspase Dronc, which is normally blocked by DIAP1. Notably, heterozygosity of yki reduced DIAP1 expression in the wing pouch, leading to elevation of Dronc activity. Dronc and JNK formed a positive-feedback loop that amplifies Dronc activation, leading to apoptosis. Our observations suggest a mechanism of robust tissue growth whereby tissues with reduced ribosomal protein prevent ectopic apoptosis via Yki activity.
Insights
Ribosomal protein gene mutations cause ribosomopathies. In flies, reduced ribosomal protein with Yki deficiency triggers JNK-mediated cell death, revealing a growth regulation mechanism.
Area of Science:
- Developmental Biology
- Genetics
- Cell Biology
Background:
- Ribosomal protein gene heterozygosity leads to ribosomopathies, but mechanisms are unclear.
- Drosophila Minute (M)/+ mutants, heterozygous for ribosomal protein genes, show developmental defects.
- Understanding these mechanisms is crucial for human developmental disorders.
Purpose of the Study:
- To investigate the mechanisms underlying developmental abnormalities caused by ribosomal protein gene heterozygosity.
- To explore the role of the Hippo pathway in ribosomopathies.
- To identify signaling pathways involved in wing growth defects in M/+ mutants.
Main Methods:
- Analysis of Drosophila Minute (M)/+ mutants and yki heterozygotes.
- Investigating wing growth, cell death, and signaling pathways (JNK, Hippo, TNF).
- Utilizing genetic manipulation and molecular analysis.
Main Results:
- M/+ flies have normal wings, but yki heterozygosity causes severe wing growth defects.
- Defects result from JNK-mediated cell death via Eiger/TNF signaling, requiring caspase Dronc.
- Yki heterozygosity reduces DIAP1, increasing Dronc activity and apoptosis.
- A positive-feedback loop between Dronc and JNK amplifies apoptosis.
Conclusions:
- Reduced ribosomal protein in M/+ mutants, combined with Yki deficiency, triggers ectopic apoptosis.
- Yki activity is essential for preventing apoptosis in tissues with reduced ribosomal protein.
- This study elucidates a mechanism for robust tissue growth regulation.
