The miR-124 family of microRNAs is critical for regeneration of the brain and visual system in the planarian Schmidtea mediterranea

Brain regeneration in planarians is mediated by precise spatiotemporal control of gene expression and is critical for multiple aspects of neurogenesis. However, the mechanisms underpinning the gene regulation essential for brain regeneration are largely unknown. Here, we investigated the role of the miR-124 family of microRNAs in planarian brain regeneration. The miR-124 family (miR-124) is highly conserved in animals and it regulates neurogenesis by facilitating neural differentiation. Yet, its role in neural wiring and brain organization is not known. In this study, we developed a novel method for delivering anti-miRs using liposomes for the functional knockdown (KD) of microRNAs. KD of Smed-miR-124 revealed a critical role for these miRNAs in neuronal organization during planarian brain regeneration. Our results also demonstrated an essential role for miR-124 in the generation of eye progenitors. Additionally, miR-124 regulates Smed-slit-1 , an axon guidance protein, either by targeting slit-1 mRNA or by potentially modulating the canonical Notch pathway. Together, our results reveal a role for miR-124 in regulating the regeneration of a functional brain and visual system.