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Nucleolin loss of function leads to aberrant Fibroblast Growth Factor signaling and craniofacial anomalies.

Authors :
Dash, Soma
Trainor, Paul A.
Source :
Development (09501991). Jun2022, Vol. 149 Issue 12, p1-14. 14p.
Publication Year :
2022

Abstract

Ribosomal RNA (rRNA) transcription and ribosome biogenesis are global processes required for growth and proliferation of all cells, yet perturbation of these processes in vertebrates leads to tissue-specific defects termed ribosomopathies. Mutations in rRNA transcription and processing proteins often lead to craniofacial anomalies; however, the cellular and molecular reasons for these defects are poorly understood. Therefore, we examined the function of the most abundant nucleolar phosphoprotein, Nucleolin (Ncl), in vertebrate development. ncl mutant (ncl-/-) zebrafish present with craniofacial anomalies such as mandibulofacial hypoplasia. We observed that ncl-/- mutants exhibited decreased rRNA synthesis and p53-dependent apoptosis, consistent with a role in ribosome biogenesis. However, we found that Nucleolin also performs functions not associated with ribosome biogenesis. We discovered that the half-life of fgf8a mRNA was reduced in ncl-/- mutants, which perturbed Fgf signaling, resulting in misregulated Sox9a-mediated chondrogenesis and Runx2-mediated osteogenesis. Consistent with this model, exogenous FGF8 treatment significantly rescued the cranioskeletal phenotype in ncl-/- zebrafish, suggesting that Nucleolin regulates osteochondroprogenitor differentiation. Our work has therefore uncovered tissue-specific functions for Nucleolin in rRNA transcription and post-transcriptional regulation of growth factor signaling during embryonic craniofacial development. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09501991
Volume :
149
Issue :
12
Database :
Academic Search Index
Journal :
Development (09501991)
Publication Type :
Academic Journal
Accession number :
157781468
Full Text :
https://doi.org/10.1242/dev.200349