Abstract
The assembly of functional neural circuits is critical for complex thoughts, behavior and general brain function. Precise construction of neural circuits requires orderly transition of sequential events from axon outgrowth, pathfinding, branching, to synaptogenesis. Each of these steps is required to be tightly regulated in order to achieve meticulous formation of neuronal connections. MicroRNAs (miRNAs), which silence gene expression post-transcriptionally via either inhibition of translation or destabilization of messenger RNAs, have emerged as key regulators of neuronal connectivity. The expression of miRNAs in neurons is often temporally and spatially regulated, providing critical timing and local mechanisms that prime neuronal growth cones for dynamic responses to extrinsic cues. Here we summarize recent findings of miRNA regulation of neuronal connectivity in a variety of experimental platforms.
Highlights
Reviewed by: Jay Gibson, The University of Texas Southwestern Medical Center, USA Federico Dajas-Bailador, University of Nottingham, UK
MiRNA REGULATION OF AXON PATHFINDING Axons are directed to their synaptic targets via the guidance of attractive or repellent cues presented in the environment www.frontiersin.org microRNAs in neuronal connectivity
Netrins are highly conserved guidance molecules that can function as both attractants and repellents in many stage-dependent biological events, such as axon guidance and motile cell migration (Hedgecock et al, 1990; Ishii et al, 1992; Chan et al, 1996; Kolodkin and Tessier-Lavigne, 2011), but the timing mechanism that controls the responsiveness of growth cones or migrating cells to Netrins at precise times is not fully understood
Summary
Reviewed by: Jay Gibson, The University of Texas Southwestern Medical Center, USA Federico Dajas-Bailador, University of Nottingham, UK. The expression of miRNAs in neurons is often temporally and spatially regulated, providing critical timing and local mechanisms that prime neuronal growth cones for dynamic responses to extrinsic cues. Precise neuronal connectivity is established through transition of sequential events from axon growth to synapse formation.
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