Excel · study · 2026
NOC4L coordinates neuronal and pharyngeal arch development by regulating ribosome biogenesis-related processes
Listed in NCBI GEO
Bowen-Conradi syndrome (BCS) is an autosomal-recessive disease marked by lethality and characterized by neurodevelopmental delays, microcephaly, and craniofacial abnormalities, yet remains mechanistically underexplored due to the absence of robust biological models.
Description
To address this gap, we generated the first vertebrate model of BCS through CRISPR-Cas9-mediated noc4l knockout in zebrafish. Our model recapitulates key clinical features observed in BCS patients, including microcephaly, micrognathia, and developmental delay.
Histopathology revealed diminished cell proliferation and elevated apoptosis within cephalic and pharyngeal arch regions of mutants. Molecular characterization revealed that rRNA processing defects impaired ribosome biogenesis, reducing 40S and 80S subunits and polysomes, ultimately leading to suppression of protein synthesis. Mechanistically, translatomic profiling identified PPARγ signaling as a significantly downregulated pathway in noc4l mutants.
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Rosiglitazone-induced PPARγ activation partially rescued cranial and pharyngeal cartilage defects, while also alleviating neurodevelopmental deficits. This work establishes impaired translational machinery as the pathogenic core of BCS and highlights PPARγ agonism as a viable therapeutic strategy, with rosiglitazone demonstrating preclinical efficacy in rescuing disease-relevant phenotypes. Our findings provide both a pathophysiological framework for BCS and a platform for testing translation-targeted interventions.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE292nnn/GSE292449 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292449 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1238785 ncbi.nlm.nih.gov/bioproject/PRJNA1238785 ↗
project · from NCBI GEO
- PubMed 41358835 pubmed.ncbi.nlm.nih.gov/41358835 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Danio rerio · Expression profiling by high throughput sequencing · Other
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE292449 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[method].geo_series_type:other | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:7955 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |