A zebrafish ribosomopathy links Ddx49-dependent ribosome biogenesis to differential failure of population expansion among pigment cell lineages
- 1University of Virginia
Abstract
Defects in ribosome biogenesis cause surprisingly cell-type specific pathologies. Why some cells are more vulnerable than others remains unresolved. Here, we show that a zebrafish pigment pattern mutant, sisley, results from a viable missense allele of ddx49, encoding a DEAD-box RNA helicase required for small ribosomal subunit biogenesis and early survival. In mutants, yellow/orange xanthophores fail to proliferate during development of the adult stripe pattern, whereas closely related melanophores are affected only mildly. The mutant protein has reduced helicase but increased ATPase activity and, consistent with impaired ribosome biogenesis in vivo, mutants are deficient in 18S rRNA relative to its precursor. Remarkably, a similar deficiency in 18S rRNA relative to precursor rRNA distinguishes xanthophores from melanophores even in the wild-type, suggesting an inherent difference in rRNA processing that leaves xanthophores vulnerable to Ddx49 dysfunction. Both xanthophore deficiency and a male-biased sex ratio of the sisley mutant were rescued by mutation of tp53. Our findings suggest how baseline differences in ribosome production shape cell-type specific outcomes of mutations affecting ribosome biogenesis, and provide an adult-viable model for Ddx49 function in vivo.
Related
- Impaired Peroxisome Import Drives Cellular Senescence through SCAF1-Dependent Suppression of Mitoribosome Biogenesis
- Differential Neurodevelopmental Toxicity of Propofol and Fospropofol: Mechanistic Insights and Potential Clinical Implications-A Zebrafish Model Study.
- Light-dependent conversion of body color change pattern during zebrafish development
- zAcademy: an open-source programmable conditioning arena reveals sex- and genotype-dependent avoidance learning in adult zebrafish
- Unpredictable chronic stress redistributes novelty-evoked exploratory space use and yields method-dependent identification of resilient-like archetypes in zebrafish
BibTeX
@misc{liang2026zebrafish,
title = {{A zebrafish ribosomopathy links Ddx49-dependent ribosome biogenesis to differential failure of population expansion among pigment cell lineages}},
author = {Y. Liang and K. Malezyna and A. J. Dennis and A. Kumar and B. McCluskey and D. S. Sepich and L. Solnica-Krezel and A. Dhayalan and A. Jomaa and L. B. Patterson and D. M. Parichy},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.13.758983},
url = {https://www.biorxiv.org/content/10.64898/2026.10.13.758983v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - A zebrafish ribosomopathy links Ddx49-dependent ribosome biogenesis to differential failure of population expansion among pigment cell lineages
AU - Y. Liang
AU - K. Malezyna
AU - A. J. Dennis
AU - A. Kumar
AU - B. McCluskey
AU - D. S. Sepich
AU - L. Solnica-Krezel
AU - A. Dhayalan
AU - A. Jomaa
AU - L. B. Patterson
AU - D. M. Parichy
PY - 2026
DA - 2026/10/13
PB - bioRxiv
DO - 10.64898/2026.10.13.758983
UR - https://www.biorxiv.org/content/10.64898/2026.10.13.758983v1
AB - Defects in ribosome biogenesis cause surprisingly cell-type specific pathologies. Why some cells are more vulnerable than others remains unresolved. Here, we show that a zebrafish pigment pattern mutant, sisley, results from a viable missense allele of ddx49, encoding a DEAD-box RNA helicase required for small ribosomal subunit biogenesis and early survival. In mutants, yellow/orange xanthophores fail to proliferate during development of the adult stripe pattern, whereas closely related melanophores are affected only mildly. The mutant protein has reduced helicase but increased ATPase activity and, consistent with impaired ribosome biogenesis in vivo, mutants are deficient in 18S rRNA relative to its precursor. Remarkably, a similar deficiency in 18S rRNA relative to precursor rRNA distinguishes xanthophores from melanophores even in the wild-type, suggesting an inherent difference in rRNA processing that leaves xanthophores vulnerable to Ddx49 dysfunction. Both xanthophore deficiency and a male-biased sex ratio of the sisley mutant were rescued by mutation of tp53. Our findings suggest how baseline differences in ribosome production shape cell-type specific outcomes of mutations affecting ribosome biogenesis, and provide an adult-viable model for Ddx49 function in vivo.
ER -