RP gene haploinsufficiency promotes extra sensory organ formation via a threshold effect

TL;DR

Reduced levels of ribosomal protein genes in fruit flies cause extra sensory organs to form when a certain threshold is crossed.

Contribution

The study reveals a threshold effect in RP gene haploinsufficiency that leads to ectopic sensory organ formation.

Findings

Strongly affected Minute mutants show a threshold-dependent increase in bristle and CS formation.

Xrp1–Irbp18 transcriptional dimer is upregulated in sensory organ-promoting Minutes.

Xrp1 mutation suppresses ectopic CS formation, indicating its regulatory role.

Abstract

Ribosomal protein (RP) gene haploinsufficiency is a conserved form of ribosome dysfunction across species and underlies a class of disorders known as ribosomopathies. In Drosophila, RP gene haploinsufficiency manifests as the Minute phenotype, characterized by thinner and shorter mechanosensory bristles. The development of both bristles and proprioceptive campaniform sensilla (CS) is initiated by the bHLH proneural proteins Achaete (Ac) and Scute (Sc). By analysing genetic interactions between ac sc mutants and Minute mutants of varying severity, we identified a novel bristle-promoting effect that occurs only in the strongly affected Minutes in which the average bristle length is shorter than a threshold. This threshold-dependent effect also promotes ectopic CS formation in the strong Minutes. Transcriptomic analyses comparing the sensory organ – promoting and non-promoting Minutes revealed significant differences in stress-response pathways, including differentially elevated expression of the Xrp1–Irbp18 transcriptional dimer. Notably, mutation of Xrp1 suppresses the ectopic CS phenotype, indicating a positive regulatory role. These findings reveal a previously unrecognized threshold effect in RP gene haploinsufficiency, in which excessive Xrp1 activity promotes supernumerary sensory organ formation, suggesting a compensatory mechanism that modulates neurogenesis under severe ribosomal stress.

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