The <i>miR-124</i> family of microRNAs is crucial for regeneration of the brain and visual system in the planarian <i>Schmidtea mediterranea</i>

Abstract

Brain regeneration in planarians is mediated by precise spatiotemporal control of gene expression and is crucial 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 <i>miR-124</i> family of microRNAs in planarian brain regeneration. The <i>miR-124</i> family (<i>miR-124</i>) is highly conserved in animals and regulates neurogenesis by facilitating neural differentiation, yet its role in neural wiring and brain organization is not known. We developed a novel method for delivering anti-miRs using liposomes for the functional knockdown of microRNAs. <i>Smed-miR-124</i> knockdown revealed a key role for these microRNAs in neuronal organization during planarian brain regeneration. Our results also demonstrated an essential role for <i>miR-124</i> in the generation of eye progenitors. Additionally, <i>miR-124</i> regulates <i>Smed-slit-1</i>, which encodes an axon guidance protein, either by targeting <i>slit-1</i> mRNA or, potentially, by modulating the canonical Notch pathway. Together, our results reveal a role for <i>miR-124</i> in regulating the regeneration of a functional brain and visual system.