Publication details
Ribosomal modifications are associated with mesenchymal fate selection in the neural crest lineage
| Authors | |
|---|---|
| Year of publication | 2026 |
| Type | Peer-reviewed scientific article |
| Magazine / Source | Nature communications |
| MU Faculty or unit | |
| Citation | |
| web | https://www.nature.com/articles/s41467-026-70375-6 |
| Doi | https://doi.org/10.1038/s41467-026-70375-6 |
| Keywords | Neural crest; tumorigenesis; neuroblastoma; sympathoadrenal development; molecular targets |
| Attached files | |
| Description | Neural crest cells contribute to craniofacial formation by differentiating into skeletogenic mesenchyme and neuro-glial lineages. Using Smart-seq2 single-cell transcriptomics, we show that mesenchymal fate commitment correlates specifically with the expression of rRNA-modifying and ribosome assembly factors, rather than structural ribosomal proteins. Notably, EMG1 and NHP2 introduce key post-transcriptional modifications into 18S rRNA, including m & sup1;acp & sup3;psi at U1248, which requires TSR3 for final maturation. Disrupting NHP2 or TSR3 in vitro and in vivo perturbs cranial neural crest differentiation; post-migratory temporal knockout of Polr1a or Polr1c also causes craniofacial malformations. These findings align with cell type-specific m & sup1;acp & sup3;psi levels during neural crest differentiation. Given the neural crest contribution to neuroblastoma, we analyze patient data to find that elevated ribosomal control and rRNA-modifying proteins predict poorer outcomes. Complementary experiments in neuroblastoma cell lines reveal functional roles for TSR3 and WDR74 in mesenchymal-like tumor states. Together, our results link rRNA modifications and ribosome assembly to fate decisions, suggesting ribosomal heterogeneity shapes both normal development and tumor progression. |
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