MicroRNA-338 modulates cortical neuronal placement and polarity

Abstract

The precise spatial and temporal regulation of gene expression orchestrates the many intricate processes during brain development. In the present study we examined the role of the brain-enriched microRNA-338 (miR-338) during mouse cortical development. Reduction of miR-338 levels in the developing mouse cortex, using a sequence-specific miR-sponge, resulted in a loss of neuronal polarity in the cortical plate and significantly reduced the number of neurons within this cortical layer. Conversely, miR-338 overexpression in developing mouse cortex increased the number of neurons, which exhibited a multipolar morphology. All together, our results raise the possibility for a direct role for this non-coding RNA, which was recently associated with schizophrenia, in the regulation of cortical neuronal polarity and layer placement.

Spatiotemporal regulation of GSK3β levels by miRNA-26a controls axon development in cortical neurons

“…Inhibition of miR-26a led to a decrease in neurons with single axonal projections, while its overexpression promoted the generation of neurons with multiple 'axon-like' neurites. In a recent study, miR-338 was shown to have a role in neuronal placement and polarisation in the cortical plate, controlling neuronal polarity, migration and/or cortical placement cues (Kos et al, 2017a). In the case of miR-26a, we show a cellautonomous role in the regulation of axon specification and growth of CNS neurons, a function that was also recently described for miR-140-3p (Ambrozkiewicz et al, 2018).…”

“…Despite this growing number of studies demonstrating the importance of miRNAs in axon and synapse development (Rajman and Schratt, 2017;Swanger and Bassell, 2011), evidence for their role in axon specification and neuronal polarisation has been largely missing. Only recently, miR-338, which was previously reported to control axonal outgrowth in cortical and superior cervical ganglion neurons (Aschrafi et al, 2008;Kos et al, 2017b), was shown to modulate cortical neuron migration and to have an effect in neuronal morphology and polarity in vivo (Kos et al, 2017a). Furthermore, a recent paper by Ambrozkiewicz et al (2018) demonstrated the capacity of miR-140 to act synergistically with its host gene E3 ubiquitin ligase WW-containing protein 2 (Wwp2) and Wwp1 in the establishment of axon-dendrite polarity of developing cortical neurons in vivo.…”

MicroRNA-338-5p alleviates neuronal apoptosis via directly targeting BCL2L11 in APP/PS1 mice

“…Although no obvious decline was observed in the expression of miR-338-5p in 10-month-old WT mice, the decline of miR-338-5p in APP/PS1 mice was accelerated, and the underlying mechanisms remains to be elucidated. The reason may be that the decreased expression of miR-338-5p was related to neuron integrity [ 18 ]. The concentration of miR-338-5p in serum has been raised as a potential diagnostic biomarker in colorectal cancer [ 39 ] and retinoblastoma [ 40 ].…”

“…As shown by the previous studies, selective overexpression or inhibition of miR-338 in cortical neuron improved or damaged the dendritic complexity and axon outgrowth [ 19 ]. Additionally, silencing miR-338-5p led to the loss of neuronal polarity and significantly decreased the number of neurons [ 18 ]. Nevertheless, it’s reported that the decreased expression of miR-338-3p correlates with neuronal survival [ 41 ].…”

“…Recently, miR-338-5p has been shown to engage in regulating neuronal placement and polarity [ 18 ] and neuronal outgrowth [ 19 ]. Moreover, increased level of miR-338-5p enhances the neuronal repair after spinal cord injury [ 20 ] and decreased expression of miR-338-5p contributes to the development of AD [ 21 ].…”