NOC4L coordinates neuronal and pharyngeal arch development by regulating ribosome biogenesis.

Overview

1. Zhanjiang Key Laboratory of Zebrafish Model for Development and Disease, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China
2. School of Medical Technology, Guangdong Medical University, Dongguan 523808, China
3. Research Center of Translational Medicine, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, China

Abstract

Mutations in ribosome biogenesis-related genes or functional defects in ribosomal proteins can lead to a class of autosomal genetic disorders characterized by tissue-specific defects, termed ribosomopathies. NOC4L, a critical factor in ribosome biogenesis, participates in the maturation of the 40S small ribosomal subunit. However, its functions in neural and cartilage development remain incompletely understood. In this study, through generation and phenotypic characterization of a zebrafish noc4l knockout model, we identified severe developmental abnormalities including microcephaly, micrognathia, and embryonic lethality. Further analyses revealed that noc4l loss-of-function results in reduced proliferation, differentiation blockade, and apoptotic activation. Mechanistically, sucrose gradient analysis demonstrated the disrupted ribosome biogenesis in noc4l mutants, with significantly reduced 40S/80S subunits and polysome levels, ultimately leading to overall translational inhibition and concurrent suppression of metabolic pathways. Pharmacological PPARγ activation via rosiglitazone partially rescued craniofacial malformations, ameliorated neurodevelopmental defects, and prolonged mutant life span. Although inhibition of the p53 pathway can partially rescue the phenotype, the p53 pathway and metabolic pathways are likely independent contributing factors. Our study reveals the molecular basis of developmental defects in noc4l mutants through impaired ribosome assembly and demonstrates the therapeutic potential of metabolic interventions for ribosomopathies.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE292449, at NCBI GEO; found in “Data availability”

Data availability

RNA-seq data and Ribo-seq data are available at Gene Expression Omnibus under accession number GSE292449 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292449).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 6 keywords, 11 MeSH terms, 3 funders, 46 references.

Cite

This paper

Song, T., Liu, Y., Zhou, Y., Li, X., Zhang, L., Ning, G., & Zhang, J. (2026). NOC4L coordinates neuronal and pharyngeal arch development by regulating ribosome biogenesis. Journal of molecular cell biology, 17(12), mjaf052. https://doi.org/10.1093/jmcb/mjaf052

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