Speaker
Description
RNA ligases play critical roles in RNA repair, splicing, and editing, but their significance in vertebrate neural development remains poorly understood. Here, we investigated RNA ligase 1 (Rlig1), a recently characterized 5’-3’ RNA ligase, using zebrafish (Danio rerio) as an in vivo model. We discovered that rlig1 mRNA is maternally deposited and later becomes enriched in the developing brain and eyes. While CRISPR/Cas9-mediated knockout of rlig1 did not lead to obvious morphological defects, mutant zebrafish exhibited impaired behavioral responses to visual stimuli. Consistent with these behavioral changes, in vivo calcium imaging revealed reduced neuronal activity in the pretectum and anterior hindbrain – key regions involved in visual processing. Notably, the number of motion-responsive neurons was significantly reduced in the anterior hindbrain of rlig1 KO larvae, while no reduction was observed in the pretectum. Despite the reduction in the anterior hindbrain, the direction selectivity of the responsive neurons was preserved. These findings suggest that Rlig1 may contribute to the establishment or maintenance of neuronal function during development. To further explore the molecular basis of this phenotype, we performed transcriptome analysis of larval heads. This revealed distinct genotype-specific expression changes in rlig1 KO larvae, including genes related to nucleotide metabolism, redox regulation, and regulated cell death pathways such as ferroptosis and necroptosis. These results suggest that Rlig1 may contribute to neuronal homeostasis during development, potentially by influencing transcript stability under metabolic or oxidative stress. By linking RNA metabolism to changes in both neural activity and gene expression, our findings open new perspectives on the molecular mechanisms that shape neural circuit functionality and sensory perception.
| Author(s) | Fiona Klusmann*, K. Slangewal, A. Kögler, A. Marx, A. Bahl, P. Müller |
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