MicroRNA function in neuronal development, plasticity and disease.
ABSTRACT The development and function of the nervous system is orchestrated by a plethora of gene regulatory mechanisms. MicroRNAs (miRNAs), an abundant class of small non-coding RNAs, are emerging as important post-transcriptional regulators of gene expression in the brain. MiRNAs function at all stages of neuronal development, ranging from the initial specification of neuronal cell types to the formation and plasticity of synaptic connections between individual neurons. Moreover, links between miRNA dysfunction and neurological diseases become more and more apparent. The study of this novel layer of gene regulation therefore promises to enrich our knowledge of brain function and pathology.
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ABSTRACT: It has been half a century since brain volume enlargement was first reported in animals reared in an enriched environment (EE). As EE animals show improved memory task performance, exposure to EE has been a useful model system for studying the effects of experience on brain plasticity. We review EE-induced neural changes in the cerebral cortex and hippocampus focusing mainly on works published in the recent decade. The review is organized in three large domains of changes: anatomical, electrophysiological, and molecular changes. Finally, we discuss open issues and future outlook towards better understanding of EE-induced neural changes.Neuroscience 09/2014; 280. DOI:10.1016/j.neuroscience.2014.09.031 · 3.33 Impact Factor
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ABSTRACT: MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to sequences within the 3' UTR of mRNAs. Because miRNAs bind to short sequences with partial complementarity, target identification is challenging. To complement the existing target prediction algorithms, we devised a systematic "reverse approach" screening platform that allows the empirical prediction of miRNA-target interactions. Using Drosophila cells, we screened the 3' untranslated regions (3' UTRs) of the Hedgehog pathway genes against a genome-wide miRNA library and identified both predicted and many nonpredicted miRNA-target interactions. We demonstrate that miR-14 is essential for maintaining the proper level of Hedgehog signaling activity by regulating its physiological target, hedgehog. Furthermore, elevated levels of miR-14 suppress Hedgehog signaling activity by cotargeting its apparent nonphysiological targets, patched and smoothened. Altogether, our systematic screening platform is a powerful approach to identifying both physiological and apparent nonphysiological targets of miRNAs, which are relevant in both normal and diseased tissues.Cell Reports 06/2014; 7(6). DOI:10.1016/j.celrep.2014.05.025 · 7.21 Impact Factor
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ABSTRACT: Abstract During early and late embryo neurodevelopment, a large number of molecules work together in a spatial and temporal manner to ensure the adequate formation of an organism. Diverse signals participate in embryo patterning and organization synchronized by time and space. Among the molecules that are expressed in a temporal and spatial manner, and that are considered essential in several developmental processes, are the microRNAs (miRNAs). In this review, we highlight some important aspects of the biogenesis and function of miRNAs as well as their participation in ectoderm commitment and their role in central nervous system (CNS) development. Instead of giving an extensive list of miRNAs involved in these processes, we only mention those miRNAs that are the most studied during the development of the CNS as well as the most likely mRNA targets for each miRNA and its protein functions.Reviews in the neurosciences 06/2014; 25(5). DOI:10.1515/revneuro-2014-0014 · 3.31 Impact Factor