Abstract

BackgroundThe small non-coding microRNAs play an important role in development by regulating protein translation, but their involvement in axon guidance is unknown. Here, we investigated the role of microRNA-134 (miR-134) in chemotropic guidance of nerve growth cones.ResultsWe found that miR-134 is highly expressed in the neural tube of Xenopus embryos. Fluorescent in situ hybridization also showed that miR-134 is enriched in the growth cones of Xenopus spinal neurons in culture. Importantly, overexpression of miR-134 mimics or antisense inhibitors blocked protein synthesis (PS)-dependent attractive responses of Xenopus growth cones to a gradient of brain-derived neurotrophic factor (BDNF). However, miR-134 mimics or inhibitors had no effect on PS-independent bidirectional responses of Xenopus growth cones to bone morphogenic protein 7 (BMP7). Our data further showed that Xenopus LIM kinase 1 (Xlimk1) mRNA is a potential target of miR-134 regulation.ConclusionsThese findings demonstrate a role for miR-134 in translation-dependent guidance of nerve growth cones. Different guidance cues may act through distinct signaling pathways to elicit PS-dependent and -independent mechanisms to steer growth cones in response to a wide array of spatiotemporal cues during development.

Highlights

  • The small non-coding microRNAs play an important role in development by regulating protein translation, but their involvement in axon guidance is unknown

  • Only BDNFinduced growth cone turning was abolished by miR-134 manipulations, suggesting that miR-134 is selectively involved in protein synthesis (PS)-dependent guidance responses

  • We found that these three microRNAs are expressed in Xenopus whole embryos and neural tubes, as well as in rat brain tissues (Figure 1A)

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Summary

Introduction

The small non-coding microRNAs play an important role in development by regulating protein translation, but their involvement in axon guidance is unknown. We examined the involvement of miRNAs in growth cone guidance responses of Xenopus neurons. We showed that the 3’ untranslated region (3’UTR) of Xenopus laevis LIMK1 (Xlimk1) mRNA could be a potential target for miR-134 binding and regulation. Together, these results support a role for miRNAs in regulation of selected guidance responses of nerve growth cones

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