Yorkie ensures robust tissue growth in Drosophila ribosomal protein mutants

Development. 2021 Jul 15;148(14):dev198705. doi: 10.1242/dev.198705. Epub 2021 Jul 27.


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.

Keywords: Cell death; Ribosomal protein mutant; Tissue growth; Yorkie.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Death
  • Down-Regulation
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Developmental
  • Inhibitor of Apoptosis Proteins / metabolism
  • Nuclear Proteins / genetics
  • Ribosomal Proteins / genetics*
  • Ribosomal Proteins / metabolism*
  • Signal Transduction
  • Trans-Activators / genetics
  • Wings, Animal / anatomy & histology
  • Wings, Animal / metabolism
  • YAP-Signaling Proteins


  • DIAP1 protein, Drosophila
  • Drosophila Proteins
  • Inhibitor of Apoptosis Proteins
  • Nuclear Proteins
  • Ribosomal Proteins
  • Trans-Activators
  • YAP-Signaling Proteins
  • Yki protein, Drosophila