A microRNA array reveals extensive regulation of microRNAs during brain development

Krichevsky, Anna M.; King, Kevin S.; Donahue, Christine P.; Khrapko, Konstantin; Kosik, Kenneth S.

doi:10.1261/rna.5980303

Cited by 964 publications

(747 citation statements)

References 34 publications

Supporting

Mentioning

719

Contrasting

Unclassified

Order By: Relevance

“…Approximately 50% of mammalian miRNAs are expressed in the brain (Krichevsky et al ., 2003; Somel et al ., 2011), many of which have critical roles in neurogenesis and neuronal development (Giraldez et al ., 2005; De Pietri Tonelli et al ., 2008). A number of hippocampal miRNAs regulate neuronal activity by targeting their downstream genes (Eacker et al ., 2011; Juhila et al ., 2011).…”

Section: Introductionmentioning

confidence: 99%

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

et al. 2016

View full text Add to dashboard Cite

SummaryHippocampal synaptic function and plasticity deteriorate with age, often resulting in learning and memory deficits. As MicroRNAs (miRNAs) are important regulators of neuronal protein expression, we examined whether miRNAs may contribute to this age‐associated decline in hippocampal function. We first compared the small RNA transcriptome of hippocampal tissues from young and old mice. Among 269 hippocampal miRNAs, 80 were differentially expressed (≥ twofold) among the age groups. We focused on 36 miRNAs upregulated in the old mice compared with those in the young mice. The potential targets of these 36 miRNAs included 11 critical Eph/Ephrin synaptic signaling components. The expression levels of several genes in the Eph/Ephrin pathway, including EphB2, were significantly downregulated in the aged hippocampus. EphB2 is a known regulator of synaptic plasticity in hippocampal neurons, in part by regulating the surface expression of the NMDA receptor NR1 subunit. We found that EphB2 is a direct target of miR‐204 among miRNAs that were upregulated with age. The transfection of primary hippocampal neurons with a miR‐204 mimic suppressed both EphB2 mRNA and protein expression and reduced the surface expression of NR1. Transfection of miR‐204 also decreased the total expression of NR1. miR‐204 induces senescence‐like phenotype in fully matured neurons as evidenced by an increase in p16‐positive cells. We suggest that aging is accompanied by the upregulation of miR‐204 in the hippocampus, which downregulates EphB2 and results in reduced surface and total NR1 expression. This mechanism may contribute to age‐associated decline in hippocampal synaptic plasticity and the related cognitive functions.

show abstract

Section: Introductionmentioning

confidence: 99%

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

et al. 2016

View full text Add to dashboard Cite

show abstract

“…miRNAs also appear to have important roles in the mammalian central nervous system (CNS). Numerous miRNAs are expressed in the CNS [22][23][24], and many neural miRNAs are expressed in spatial and/or temporal patterns that suggest roles in the regulation of CNS development [25][26][27][28][29][30]. MiRNA miR-132 has been shown to regulate neuronal morphogenesis through decreasing levels of GTPase-activating protein, p250GAP [31] and (along with miR-219) has been implicated in the regulation of circadian rhythms [32].…”

Section: Introductionmentioning

confidence: 99%

“…MiR-134 has been shown to regulate dendritic spine development by inhibiting expression of the Limk1 protein kinase [34]. miR-124 is one of the most abundantly expressed miRNAs in the nervous system, being widely expressed in neurons in the brain, retina, and spinal cord [22,25,26,28,[35][36][37]. There are three miR-124 genes, miR-124-1, miR-124-2, and miR-124-3, located on three different chromosomes in mouse and human genomes [38].…”

Section: Introductionmentioning

confidence: 99%

“…All three miR-124 genes are widely expressed in overlapping patterns in the mouse nervous system [28]. The expression of mammalian miR-124 can be first detected in differentiating neurons and persists in mature neurons, suggesting that miR-124 plays important roles during neural development [25,28,37,39,40]. The expression of miR-124 appears in part to mediate the repression of non-neuronal genes in neurons [41][42][43], as well as the downregulation of genes expressed in neural progenitors [44].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation

Chung

Deo

et al. 2008

Experimental Cell Research

287

207

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are small RNAs with diverse regulatory roles. The miR-124 miRNA is expressed in neurons in the developing and adult nervous system. Here we show that overexpression of miR-124 in differentiating mouse P19 cells promotes neurite outgrowth, while blocking miR-124 function delays neurite outgrowth and decreases acetylated α-tubulin. Altered neurite outgrowth also was observed in mouse primary cortical neurons when miR-124 expression was increased, or when miR-124 function was blocked. In uncommitted P19 cells, miR-124 expression led to disruption of actin filaments and stabilization of microtubules. Expression of miR-124 also decreased Cdc42 protein and affected the subcellular localization of Rac1, suggesting that miR-124 may act in part via alterations to members of the Rho GTPase family. Furthermore, constitutively active Cdc42 or Rac1 attenuated neurite outgrowth promoted by miR-124. To obtain a broader perspective, we identified mRNAs downregulated by miR-124 in P19 cells using microarrays. mRNAs for proteins involved in cytoskeletal regulation were enriched among mRNAs downregulated by miR-124. A miR-124 variant with an additional 5' base failed to promote neurite outgrowth and downregulated substantially different mRNAs. These results indicate that miR-124 contributes to the control of neurite outgrowth during neuronal differentiation, possibly by regulation of the cytoskeleton.

show abstract

“…MicroRNAs (miRNAs) are small, noncoding transcripts, and 22 nucleotides long, which belong to a regulatory class of RNAs that repress expression of target mRNAs (Bak et al, 2008;Krichevsky et al, 2003Krichevsky et al, , 2006Miska et al, 2004). miRNAs have been shown to be a driving force in embryonic development in multiple species (such as zebrafish, xenopus, and mouse) (Foshay and Gallicano, 2009;Leucht et al, 2008) and have distinct expression patterns within the developing brain and CNS (Bak et al, 2008).…”

Section: Mirna Misregulation and Ntdsmentioning

confidence: 99%

A new perspective on neural tube defects: Folic acid and microRNA misexpression

Shookhoff

Gallicano

2010

Genesis

View full text Add to dashboard Cite

Summary: Neural tube defects (NTDs) are the second most common birth defects in the United States. It is well known that folic acid supplementation decreases about 70% of all NTDs, although the mechanism by which this occurs is still relatively unknown. The current theory is that folic acid deficiency ultimately leads to depletion of the methyl pool, leaving critical genes unmethylated, and, in turn, their improper expression leads to failure of normal neural tube development. Recently, new studies in human cell lines have shown that folic acid deficiency and DNA hypomethylation can lead to misexpression of microRNAs (miRNAs). Misexpression of critical miRNAs during neural development may lead to a subtle effect on neural gene regulation, causing the sometimes mild to severely debilitating range of phenotypes exhibited in NTDs. This review seeks to cohesively integrate current information regarding folic acid deficiency, methylation cycles, neural development, and miRNAs to propose a potential model of NTD formation. In addition, we have examined the relevant gene pathways and miRNAs that are predicted to affect them, and based on our investigation, we have devised a basic template of experiments for exploring the idea that miRNA misregulation may be linked to folic acid deficiency and NTDs. genesis 48:282-294, 2010. V V C 2010 Wiley-Liss, Inc.

show abstract

A microRNA array reveals extensive regulation of microRNAs during brain development

Cited by 964 publications

References 34 publications

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

miR‐204 downregulates EphB2 in aging mouse hippocampal neurons

MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation

A new perspective on neural tube defects: Folic acid and microRNA misexpression

Contact Info

Product

Resources

About