MicroRNA expression in the adult mouse central nervous system - PubMed (original) (raw)

Comparative Study

MicroRNA expression in the adult mouse central nervous system

Mads Bak et al. RNA. 2008 Mar.

Abstract

MicroRNAs are approximately 22 nucleotide endogenous noncoding RNAs that post-transcriptionally repress expression of protein-coding genes by base-pairing with the 3'-untranslated regions of the target mRNAs. We present here an inventory of miRNA expression profiles from 13 neuroanatomically distinct areas of the adult mouse central nervous system (CNS). Microarray profiling in combination with real-time RT-PCR and LNA (locked nucleic acid)-based in situ hybridization uncovered 44 miRNAs displaying more than threefold enrichment in the spinal cord, cerebellum, medulla oblongata, pons, hypothalamus, hippocampus, neocortex, olfactory bulb, eye, and pituitary gland. These findings suggest that a large number of mouse CNS-expressed miRNAs may be associated with specific functions within these regions. Notably, more than 50% of the identified mouse CNS-enriched miRNAs showed different expression patterns compared to those reported in zebrafish, although the mature miRNA sequences are nearly 100% conserved between the two vertebrate species. The inventory of miRNA profiles in the adult mouse CNS presented here provides an important step toward further elucidation of miRNA function and miRNA-related gene regulatory networks in the mammalian central nervous system.

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Figures

FIGURE 1.

FIGURE 1.

(A) Ubiquitously expressed miRNAs in the mouse central nervous system. Heat map of 45 miRNAs showing highest expression across all CNS regions including whole brain. (B) Region-specific miRNA expression in the adult mouse central nervous system identified by SAM analysis (FDR = 0). (Pit) Pituitary; (Ob) olfactory bulb; (Mo) medulla oblongata; (Sc) spinal cord; (Hip) hippocampus; (Cer) cerebellum; (Pon) pons; (Hyp) hypothalamus; (Ctx) cortex; (Amy) amygdala; (Mes) mesencephalon; (Tha) thalamus; (Brain) whole brain.

FIGURE 2.

FIGURE 2.

Regionally enriched miRNAs in the mouse central nervous system. Heat maps of miRNAs displaying more than threefold enrichment in 10 areas of the adult mouse CNS compared to their average expression levels in all 13 regions (P < 0.05) as identified by multiclass SAM analysis (FDR = 0) followed by multiple one-sample _t_-tests. _P_-values were adjusted for multiple comparisons using the Bonferroni procedure. Shown are the average ratios of three replica hybridizations. (Pit) pituitary; (Ob) olfactory bulb; (Mo) medulla oblongata; (Sc) spinal cord; (Hip) hippocampus; (Cer) cerebellum; (Pon) pons; (Hyp) hypothalamus; (Ctx) neocortex; (Amy) amygdala; (Mes) mesencephalon; (Tha) thalamus; (B) whole brain.

FIGURE 3.

FIGURE 3.

microRNA expression in the adult mouse CNS assessed by miRNA-specific (A–G) real-time RT-PCR and (H–K) in situ hybridization. Expression of (A) miR-7, (B) miR-218, (C) miR-34a, (D) miR-7b, (E) miR-429, (F) miR-96, and (G) miR-25 in different adult mouse CNS regions relative to whole brain was determined by miRNA-specific real-time RT-PCR assays. Error bars of real-time RT-PCR data indicate the standard error of the mean of three biological replicates; error bars of microarray data indicate the standard error of the mean of three replica hybridizations. Heat maps below bar diagrams show the microarray expression profile for each investigated miRNA. Stars in heat maps indicate the brain areas in which the miRNA was enriched. Expression of (H) miR-128, (I) miR-200b, (J) miR-195, and (K) miR-218 detected by LNA-based in situ hybridization on saggital sections of the adult mouse brain. miR-128 is expressed in the neocortex, striatum, thalamus, hippocampus, and the cerebellum (H). (I, inset) LNA-ISH of miR-200b on a coronal section of the olfactory bulb. (I) miR-200b is highly expressed in the olfactory bulb as compared to other regions. (J) The strongest in situ hybridization signal for miR-195 was detected in the cerebellum, whereas (K) in situ detection of miR-218 showed weak expression in most regions. (Pit) pituitary; (Ob) olfactory bulb; (Mo) medulla oblongata; (Sc) spinal cord; (Hip) hippocampus; (Cer) cerebellum; (Pon) pons; (Hyp) hypothalamus; (Ctx) neocortex; (Amy) amygdala; (Mes) mesencephalon; (Tha) thalamus; (B) whole brain.

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