A Novel MicroRNA-Odorant Receptor Axis Governs Neural Progenitor Cell Proliferation in Zebrafish CNS

Abstract

Spinal cord injury causes irreversible neurological deficits in mammals; yet zebrafish achieve complete functional recovery through molecular mechanisms that remain poorly defined. In this study we emphasized on a critical miRNA-mediated regulation of Ependymo-radial glial (ERG) cell proliferation in zebrafish spinal cord. Using next-generation sequencing we constructed a spatiotemporal miRNA profile across multiple post-injury time points and identified dre-miR-N1 as a novel injury-responsive miRNA involved in ERG proliferation among several differentially expressed novel miRNAs. Fluorescent in situ hybridization confirmed its robust lesion-site expression and gain-of-function analysis demonstrated that dre-miR-N1 significantly impaired functional recovery. Target prediction and validation unexpectedly identified the odorant receptor gene or42a1 as a high-confidence target and a combinatorial approach of miRNA gain-of-function and or42a1 loss-of-function showed that dre-miR-N1 modulates the proliferative behaviour of or42a1-expressing ERG cells under both homeostatic and injury conditions. These findings uncover a previously unrecognized miRNA-odorant receptor axis governing injury-induced ERG cell expansion establishing a novel molecular framework for endogenous neural regeneration in zebrafish.