Identification of Alternative Splicing and LncRNA Genes in Brain Tissues of Fetal Mice at Different Developmental Stages

Abstract

Background: Brain development is an extremely complex and precisely regulated process, with about one-third of genes expressed and precisely regulated during brain development. Objective:: This study aims to explore the molecular mechanisms involved in brain development. Methods: We first established the expression profile of long non-coding RNAs (lncRNAs) and mRNAs in brain tissues of fetal mice at 12.5d, 14.5d and 16.5d through high-throughput sequencing. Second, the associated functions, pathways, and networks of the co-differentially expressed lncRNAs and mRNAs were identified via Gene Ontology (GO), pathway analysis, and PPI network. After bioinformatic analysis and screening, 8 differentially expressed lncRNAs and mRNAs with the same genetic origin were verified by RT-qPCR analysis in brain tissues of fetal mice at different developmental stages. Results: The data revealed that there were 972 co-differentially expressed lncRNAs and 992 codifferentially expressed mRNAs in brain tissues of fetal mice at 12.5d, 14.5d and 16.5d. And we discovered 125 differentially expressed lncRNAs and mRNAs, which have the same genetic origin, in brain tissues of fetal mice at 12.5d, 14.5d and 16.5d through sequencing results and bioinformatics analysis. Besides, we proved that 8 lncRNAs, which have had the same genetic origin as differentially expressed mRNAs, were prominently downregulated, while their maternal genes were upregulated during brain development in fetal mice. Conclusion: Our results preliminarily illustrated the differentially expressed lncRNAs and mRNAs, both of which were derived from the same parent genes, during brain development in fetal mice, which suggests that alternative splicing of lncRNA exists during brain development. Besides, our study provides a perspective on critical genes for brain development, which might be the underlying therapeutic targets for developmental brain diseases in children.