Regulation of chemotropic guidance of nerve growth cones by microRNA

We 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.These 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.Developing axons are guided to their specific targets for complex neuronal connections by a spatiotemporal pattern of extracellular cues [1,2]. The motile tip of the axons, the growth cone, reacts to various guidance molecules with distinct responses, including acceleration of extension, inhibition and/or collapse of growth cones, and turning towards or away from attractive or repulsive cues [2,3]. Recent studies have shown that local protein synthesis and degradation play a role in axon guidance [4-9]. However, the mechanisms underlying protein synthesis (PS)-dependent regulation of growth cone guidance remain to be fully elucidated. In addition to the classical translation mechanism involving the mammalian target of rapamycin (mTOR) [6,10,11], increasing evidence indicates that microRNAs (miRNAs), the non-coding RNAs of ~20-23 bps, regulate mRNA expression [12-14]. MiRNAs often bind to target mRNAs through partial complementary pairing to suppress mRNA translation or decrease mRNA