In humans, heterozygous mutations of ribosomal proteins can cause severe developmental defects, such as Diamond–Blackfan anaemia. In contrast, the DrosophilaMinute mutants, which may carry any one of a selection of ribosomal protein mutations, are phenotypically largely normal, suggesting they have mechanisms to counteract the loss of ribosomal protein activity. Now, Tatsushi Igaki and colleagues investigate the mechanisms by which Drosophila maintains morphogenesis in Minute mutants. Using a genetic screen, they find that heterozygosity for the Hippo pathway effector Yki leads to severe developmental defects in a background of heterozygous RpS3 (RpS3/+) or other ribosomal proteins. These defects are primarily caused by increased rates of apoptosis along the anteroposterior boundary in the wing discs of RpS3/+ yki/+ flies, which result from elevated JNK signalling. The authors further reveal that the caspase inhibitor DIAP1, a Yki target, shows reduced expression in the posterior compartment of RpS3/+ yki/+ wing discs. Indeed, Diap1 knockdown in the posterior or entire wing disc is sufficient to cause morphological defects in an RpS3/+ background, indicating that DIAP1 expression is the critical function of Yki in maintaining normal morphogenesis in Minute mutants. Collectively, these findings suggest that safeguarding against increased apoptosis may be a crucial step in preventing developmental defects in Minute mutants, a hypothesis that can now be investigated further in humans.
