Regulation of chemotropic guidance of nerve growth cones by microRNA

Mol Brain. 2011 Nov 3:4:40. doi: 10.1186/1756-6606-4-40.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Chemotaxis* / drug effects
  • Fluorescent Antibody Technique
  • Gene Expression Regulation / drug effects
  • Growth Cones / drug effects
  • Growth Cones / enzymology
  • Growth Cones / metabolism*
  • Humans
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Models, Biological
  • Oligonucleotides, Antisense / pharmacology
  • Phosphorylation / drug effects
  • Xenopus
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • MicroRNAs
  • Oligonucleotides, Antisense
  • Xenopus Proteins
  • Mitogen-Activated Protein Kinase 1