Abstract
BackgroundSynapse formation and the development of neural networks are known to be controlled by a coordinated program of mRNA synthesis. microRNAs are now recognized to be important regulators of mRNA translation and stability in a wide variety of organisms. While specific microRNAs are known to be involved in neural development, the extent to which global microRNA and mRNA profiles are coordinately regulated in neural development is unknown.ResultsWe examined mouse primary neuronal cultures, analyzing microRNA and mRNA expression. Three main developmental patterns of microRNA expression were observed: steady-state levels, up-regulated and down-regulated. Co-expressed microRNAs were found to have related target recognition sites and to be encoded in distinct genomic locations. A number of 43 differentially expressed miRNAs were located in five genomic clusters. Their predicted mRNA targets show reciprocal levels of expression. We identified a set of reciprocally expressed microRNAs that target mRNAs encoding postsynaptic density proteins and high-level steady-state microRNAs that target non-neuronal low-level expressed mRNAs.ConclusionWe characterized hundreds of miRNAs in neuronal culture development and identified three major modes of miRNA expression. We predict these miRNAs to regulate reciprocally expressed protein coding genes, including many genes involved in synaptogenesis. The identification of miRNAs that target mRNAs during synaptogenesis indicates a new level of regulation of the synapse.
Highlights
Synapse formation and the development of neural networks are known to be controlled by a coordinated program of mRNA synthesis. microRNAs are recognized to be important regulators of mRNA translation and stability in a wide variety of organisms
Coordinated waves of mRNA expression are well described during embryonic development [3] including in brain development and synaptogenesis in vitro [4,5] and many genes may be targets for miRNAs
Results mRNA Expression Analysis Previous studies of neuronal network activity in mouse E17.5 primary neuronal cultures established that spontaneous firing arises after three to six days and that during this phase there is a wave of synthesis of mRNAs encoding synaptic proteins [4]
Summary
Synapse formation and the development of neural networks are known to be controlled by a coordinated program of mRNA synthesis. microRNAs are recognized to be important regulators of mRNA translation and stability in a wide variety of organisms. Synapse formation and the development of neural networks are known to be controlled by a coordinated program of mRNA synthesis. MicroRNAs (miRNAs) are known to regulate the expression of target genes both at the level of mRNA translation and mRNA stability [1,2]. This ability to influence multiple genes makes miRNAs well suited for the regulation of systems where the expression of large numbers of genes changes in concert. The period of neurogenesis between embryonic days 9-17 is followed by postmitotic neurons extending neurites and forming synapses and networks [10]. Whole genome mRNA profiling of primary cultures from E17.5 embryos over three (page number not for citation purposes)
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