Fig 9

Summary of the consequences of polr3a^sa907 in zebrafish development.
At 2 dpf, no morphological differences are apparent in polr3a^sa907/sa907 zebrafish and neural crest cells (NCC) develop normally. However, at this same stage, slight reductions are observed in pre-tRNA transcription. By 3 dpf, after depletion of maternal stores, polr3a^sa907/sa907 zebrafish show increased cell death and reduced proliferation, which contributes to a global reduction in growth. Increased cell death is also observed in the developing craniofacial cartilage and scRNA-seq revealed elevated expression of the tp53 pathway in the cartilage. Increased tp53 is also observed in some other cell types, contributing to overall cranial development (dashed arrow). On the molecular side, by 3 dpf, transcription of pre-tRNAs is significantly reduced, as are other genes transcribed by Pol III including 7SL RNA. A slight reduction in 5’ETS rRNA transcribed by Pol I is also observed. Combined, this leads to an overall reduction in ribosome biogenesis at 5 dpf. Developmentally, at 5 dpf, there are measurable differences in the craniofacial cartilage and bone, with reductions in all elements examined. These differences persist through 8 dpf, which is the limit of the lifespan of polr3a^sa907/sa907 zebrafish. Created in BioRender. Watt, K. (2026) https://BioRender.com/ni7bxps.