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

Vidyanand Sasidharan,Nishtha Nayyar,Alejandro Sánchez Alvarado,Dasaradhi Palakodeti,Vairavan Lakshmanan,Praveen Kumar Vemula,Dhiru Bansal,Sarah A Elliott,Srishti Baid,Srujan Marepally

doi:10.1242/dev.144758

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 miR-124 family of microRNAs in planarian brain regeneration. The miR-124 family (miR-124) 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. Smed-miR-124 knockdown revealed a key role for these microRNAs 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, which encodes an axon guidance protein, either by targeting slit-1 mRNA or, potentially, by 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.

Highlights

Brain wiring is a complex process that ensures the formation of an intricate network of intercommunicating neurons
Since wholemount in situ hybridization (WISH) revealed that the miR-124 family is enriched in the nervous system of the adult planarian (Gonzalez-Estevez et al, 2009; Sasidharan et al, 2013), we aimed to explore the function of this family, including its potential roles in neurogenesis
WISH using locked nucleic acid (LNA) detection probes confirmed the expression of miR-124a, b and c in the cephalic ganglia and ventral nerve cords (Fig. S1A)

Summary

Introduction

Brain wiring is a complex process that ensures the formation of an intricate network of intercommunicating neurons. The differentiating primordia of the brain and eyes are evident ∼3 days post-amputation (dpa), the recovery of the functional brain is completed only after 7 dpa (Inoue et al, 2004; Ong et al, 2016) Axon guidance proteins, such as those encoded by members of the dscam, slit, netrin and robo families, are essential for neural regeneration in planarians, and these factors are required for the patterning of the brain (Agata and Umesono, 2008; Yamamoto and Agata, 2011; Fusaoka et al, 2006; Cebria et al, 2007; Beane et al, 2012). The factors that regulate the spatiotemporal expression of these genes, which are crucial for the proper patterning of the planarian visual system and brain, are not known

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