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Transcriptome analysis of mouse cortical development and characterization of long non-coding RNAs

ABSTRACT: Cortical neural progenitor cells (NPCs) change their competency over time during development, giving rise to distinct cell types sequentially. Many genes that govern cortical development are now known, but it remains elusive how their temporal expression is controlled. Recently, long non-coding RNAs are found to be essential for cell-fate specification and precise gene regulation in many developmental events. In this study, strand-specific RNA sequencing studies unveil large amount of long non-coding RNAs are actively and differentially expressed across mouse cortical development. Integration of RNA sequencing data from key stages of developing mouse cortex enables us to cluster coding and non-coding transcripts into co-expression “modules” to infer functional relationships. Intriguingly, the cortical transcriptome undergoes significant changes in early mouse neurogenesis. Cortical long non-coding RNAs tends to be transcribed from genomic loci adjacent to protein-coding genes related to neural development. Finally, we found large amount of predicted enhancer regions are able to transcribe RNAs. This study will help us better understand molecularly how cortical NPCs specify their fates during development, especially roles of lncRNAs in this process.

ORGANISM(S): Mus musculus

PROVIDER: GSE55600 | GEO | 2019/02/26

REPOSITORIES: GEO

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Project description:Neurogenesis is a pro-survival process that comprises of dendritic and axonal growth, synaptogenesis, synaptic and neuronal pruning. These complex processes are determined by temporal gene expression during development, which is in turn tightly regulated by long non-coding RNAs and microRNAs. In this study, we investigated the processes implicated in the maturation of primary neuronal cultures based on RNA expression profiling. Correlation between neuron specific gene ontologies of mRNA and non-coding RNAs identified direct regulation of axonogenesis and dendritogenesis. Temporally regulated mRNA and their associated long non-coding RNAs were significantly overrepresented in proliferation and differentiation associated signalling, cell adhesion molecules and neurotrophin signalling pathways during neuronal maturation. Long non-coding RNAs associated with Axin2, Cntn1, Ncam1, Negr1, Ntrk2, Nrxn1 and Sh2b3 displayed an inverse expression profile to their mRNA whereas long non-coding RNA -mRNA pairs for Kit, Prkcb and Ralgds displayed similar expression profiles. These genes were also predicted targets of the altered miRNAs, miR-124, -128, -129-5p, -203, -218, -290-5p, -326, -329, -377 and -495. These microRNAs particularly regulate the cell adhesion molecules, Cntn1, Ncam1, Negr1 and Nrxn1 that determine axonogenesis and dendritogenesis, supporting the observed co-regulation of these biological processes by non-coding RNAs. Verification of expression of these long non-coding RNA-mRNA pairs in an in vitro model of ischemic-reperfusion injury showed an inverse expression profile, thus confirming their role(s) in maintenance of the neuronal structure and function. This neuronal transcriptome (mRNAs, lncRNAs, miRNAs) is in turn orchestrated by C/EBPM-NM-1/M-NM-2 transcription factors and CTCF, thereby governing intricate control of neuronal development. microRNA expression profiling of maturing primary cortical neurons from E15 mouse embryos. Maturing neurons were harvested on Days 2, 4, 6 and 8.

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Transcriptome analysis of mouse cortical development and characterization of long non-coding RNAs

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