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Regulation of chemotropic guidance of nerve growth cones by microRNA.


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Authors

Han, Liang 
Wen, Zhexing 
Lynn, Rachel C 
Baudet, Marie-Laure 
Holt, Christine E 

Abstract

BACKGROUND: The 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. RESULTS: 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. CONCLUSIONS: 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.

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Keywords

Animals, Brain-Derived Neurotrophic Factor, Chemotaxis, Fluorescent Antibody Technique, Gene Expression Regulation, Growth Cones, Humans, MicroRNAs, Mitogen-Activated Protein Kinase 1, Models, Biological, Oligonucleotides, Antisense, Phosphorylation, Xenopus, Xenopus Proteins

Journal Title

Mol Brain

Conference Name

Journal ISSN

1756-6606
1756-6606

Volume Title

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (085314/Z/08/Z)