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Published on: April 22, 2019
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A CRISPR-Cas9 mutation in sox9b long intergenic noncoding RNA (slincR) affects zebrafish development, behavior, and
Subham Dasgupta1, Jane K LaDu1, Gloria R Garcia1
1Sinnhuber Aquatic Research Laboratory, Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97333, USA.
Summary
A new zebrafish model reveals that the long noncoding RNA (lncRNA) slincR plays a crucial role in development and toxicological responses. Disrupting slincR impacts gene expression, cartilage development, and tail fin regeneration, highlighting its endogenous functions.
Area of Science:
- Toxicology and developmental biology
- Genetics and molecular biology
- Environmental health sciences
Background:
- Long noncoding RNAs (lncRNAs) are increasingly recognized as regulators of toxicological responses to environmental chemicals.
- The aryl hydrocarbon receptor (AHR) pathway is a key mediator of responses to environmental toxins like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
- Our lab previously identified slincR, an lncRNA activated by AHR ligands.
Purpose of the Study:
- To investigate the biological function of slincR using a CRISPR-Cas9-mediated zebrafish mutant line.
- To assess the impact of slincR disruption on toxicological responses to TCDD.
- To explore the endogenous role of slincR in development and regeneration.
Main Methods:
- Generation of a CRISPR-Cas9 slincR mutant zebrafish line (slincRosu3) with an 18 bp insertion.
- Toxicological profiling of slincRosu3 mutants exposed to TCDD.
- Embryonic mRNA sequencing to analyze gene expression changes.
- Assessment of cartilage development and tail fin regeneration capacity.
Main Results:
- slincRosu3 mutants showed equal or greater sensitivity to TCDD-induced morphological and behavioral changes.
- mRNA sequencing revealed differential gene expression in slincRosu3 mutants, with 499 or 908 genes affected with or without TCDD exposure.
- Unexposed slincRosu3 embryos exhibited disruptions in metabolic pathways and repressed sox9b-a mRNA levels.
- Cartilage development was impaired, and tail fin regeneration capacity was lost in slincRosu3 embryos, with reduced cell proliferation.
Conclusions:
- A mutation in slincR significantly impacts endogenous gene expression and structural development.
- slincR plays a critical role in cartilage development and regenerative capacity.
- slincR has limited but significant impacts on AHR induction responses, underscoring its importance in developmental processes.
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