MicroRNAs contribute to postnatal development of laminar differences and neuronal subtypes in the rat medial entorhinal cortex

Abstract

The medial entorhinal cortex (MEC) is important in spatial navigation and memory formation and its layers have distinct neuronal subtypes, connectivity, spatial properties, and disease susceptibility. As little is known about the molecular basis for the development of these laminar differences, we analyzed microRNA (miRNA) and messenger RNA (mRNA) expression differences between rat MEC layer II and layers III–VI during postnatal development. We identified layer and age-specific regulation of gene expression by miRNAs, which included processes related to neuron specialization and locomotor behavior. Further analyses by retrograde labeling and expression profiling of layer II stellate neurons and in situ hybridization revealed that the miRNA most up-regulated in layer II, miR-143, was enriched in stellate neurons, whereas the miRNA most up-regulated in deep layers, miR-219-5p, was expressed in ependymal cells, oligodendrocytes and glia. Bioinformatics analyses of predicted mRNA targets with negatively correlated expression patterns to miR-143 found that miR-143 likely regulates the Lmo4 gene, which is known to influence hippocampal-based spatial learning.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-017-1389-z) contains supplementary material, which is available to authorized users.

MicroRNA Profiling Shows a Time-Dependent Regulation within the First 2 Months Post-Birth and after Mild Neonatal Hypoxia in the Hippocampus from Mice

“…Whilst, neurogenesis is more prominent during prenatal development, glia-genesis mainly occurs during postnatal development. In our study and previously, miR-20a was observed to be downregulated over time [ 26 ]. MiR-20a is critical for brain maturation during embryogenesis by regulating axonal growth and dendritogenesis, and its expression is time-dependent [ 30 ].…”

“…Corroborating these results, previous studies analyzed the role of microRNAs on the development of the layers of the medial entorhinal cortex postnatally, and age-specific microRNA regulation was identified in rats [ 26 ]. MiR-20a, miR-29c, miR-132 and miR-219-5p in particular, were found to be up-regulated in the medial entorhinal cortex, suggesting that these microRNAs may be crucial for neuronal and glial maturation postnatally, including neuronal maturation, dendritic spines morphology and inhibit apoptosis in neurons [ 27 , 28 ], interestengly miR-219 has a key role on myelin formation by regulating oligodendrocytes maturation [ 29 ].…”

“…Further studies should evaluate sex differences during postnatal brain development to evaluate the effect of sex in microRNA expression. Finally, we focus on the hippocampus, a vulnerable region to hypoxia, similar changes in specific microRNAs have been seen in other brain regions, e.g., entorhinal cortex [ 26 ], we can speculate that common mechanisms are activated independent of the region, however, it will be necessary to evaluate their regulation in parallel to determine if the time scale of brain maturation is similar.…”

Microcircuits for spatial coding in the medial entorhinal cortex

“…In general, classification of cell types remains an important challenge for the future, both for interneurons and principal cells (Figure 3). It has not been possible thus far to directly relate anatomically-and functionally-defined cell types, in large part because there is no straightforward link between anatomical (molecular expression profile, hodology, morphology, layer, brain region) and intrinsic physiological properties (11,80,211,212,265,(319)(320)(321). Adding further complexity, pyramidal cells in different MEC layers and even different parahippocampal areas can have similar functional properties (136,138), and there can be substantial variability of function for any particular anatomically defined cell type both within and between animals [e.g.…”

Comprehensive transcriptomic analyses of tissue, serum, and serum exosomes from hepatocellular carcinoma patients

“…TargetScan gave us ~ 8500 unique target genes for these miRNAs. We further filtered the number of miRNA-target gene pairs based on expression levels of miRNA (keeping highly expressed miRNAs having 75% percentile expression across samples > 10 log 2 cpm), weighted context scores from TargetScan (less than − 0.4) and selecting the miRNA target gene pairs, if more than 75% of the number of miRNAs targeting one gene are either all up or all downregulated [35]. Further, we selected only the negatively correlated miRNA-target gene pairs.…”