Dataset Information

Spatio-temporal and dynamic regulation of neurofascin alternative splicing in mouse cerebellar neurons.

ABSTRACT: Alternative splicing is crucial for molecular diversification, which greatly contributes to the complexity and specificity of neural functions in the central nervous system (CNS). Neurofascin (NF) is a polymorphic cell surface protein that has a number of splicing isoforms. As the alternative splicing of the neurofascin gene (Nfasc) is developmentally regulated, NF isoforms have distinct functions in immature and mature brains. However, the molecular mechanisms underlying the alternative splicing of Nfasc in neurons are not yet understood. Here, we demonstrate that, alongside developmental regulation, Nfasc alternative splicing is spatially controlled in the mouse brain. We then identified distinct Nfasc splicing patterns at the cell-type level in the cerebellum, with Nfasc186 being expressed in Purkinje cells and absent from granule cells (GCs). Furthermore, we show that high K+-induced depolarization triggers a shift in splicing from Nfasc140 to Nfasc186 in cerebellar GCs. Finally, we identified a neural RNA-binding protein, Rbfox, as a key player in neural NF isoform selection, specifically controlling splicing at exons 26-29. Together, our results show that Nfasc alternative splicing is spatio-temporally and dynamically regulated in cerebellar neurons. Our findings provide profound insight into the mechanisms underlying the functional diversity of neuronal cell-adhesive proteins in the mammalian CNS.

SUBMITTER: Suzuki S

PROVIDER: S-EPMC5595909 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Spatio-temporal and dynamic regulation of neurofascin alternative splicing in mouse cerebellar neurons.

Suzuki Satoko S Ayukawa Noriko N Okada Chisa C Tanaka Masami M Takekoshi Susumu S Iijima Yoko Y Iijima Takatoshi T

Scientific reports 20170912 1

Alternative splicing is crucial for molecular diversification, which greatly contributes to the complexity and specificity of neural functions in the central nervous system (CNS). Neurofascin (NF) is a polymorphic cell surface protein that has a number of splicing isoforms. As the alternative splicing of the neurofascin gene (Nfasc) is developmentally regulated, NF isoforms have distinct functions in immature and mature brains. However, the molecular mechanisms underlying the alternative splicin ...[more]

PMID: 28900163

Similar Datasets

Project description:Alternative splicing is pervasive in mammalian genomes and involved in embryo development, whereas research on crosstalk of alternative splicing and embryo development was largely restricted to mouse and human and the alternative splicing regulation during embryogenesis in zebrafish remained unclear. We constructed the alternative splicing atlas at 18 time-course stages covering maternal-to-zygotic transition, gastrulation, somitogenesis, pharyngula stages, and post-fertilization in zebrafish. The differential alternative splicing events between different developmental stages were detected. The results indicated that abundance alternative splicing and differential alternative splicing events are dynamically changed and remarkably abundant during the maternal-to-zygotic transition process. Based on gene expression profiles, we found splicing factors are expressed with specificity of developmental stage and largely expressed during the maternal-to-zygotic transition process. The better performance of cluster analysis was achieved based on the inclusion level of alternative splicing. The biological function analysis uncovered the important roles of alternative splicing during embryogenesis. The identification of isoform switches of alternative splicing provided a new insight into mining the regulated mechanism of transcript isoforms, which always is hidden by gene expression. In conclusion, we inferred that alternative splicing activation is synchronized with zygotic genome activation and discovered that alternative splicing is coupled with transcription during embryo development in zebrafish. We also unveiled that the temporal expression dynamics of splicing factors during embryo development, especially co-orthologous splicing factors. Furthermore, we proposed that the inclusion level of alternative splicing events can be employed for cluster analysis as a novel parameter. This work will provide a deeper insight into the regulation of alternative splicing during embryogenesis in zebrafish.

Project description:Both transcription and post-transcriptional processes, such as alternative splicing, play crucial roles in controlling developmental programs in metazoans. Recently emerged RNA-seq method has brought our understanding of eukaryotic transcriptomes to a new level, because it can resolve both gene expression level and alternative splicing events simultaneously. To gain a better understanding of cellular differentiation in gonads, we analyzed mRNA profiles from Drosophila testes and ovaries using RNA-seq. We identified a set of genes that have sex-specific isoforms in wild-type (WT) gonads, including several transcription factors. We found that differentiation of sperms from undifferentiated germ cells induced a dramatic downregulation of RNA splicing factors. Our data confirmed that RNA splicing events are significantly more frequent in the undifferentiated cell-enriched bag of marbles (bam) mutant testis, but downregulated upon differentiation in WT testis. Consistent with this, we showed that genes required for meiosis and terminal differentiation in WT testis were mainly regulated at the transcriptional level, but not by alternative splicing. Unexpectedly, we observed an increase in expression of all families of chromatin remodeling factors and histone modifying enzymes in the undifferentiated cell-enriched bam testis. More interestingly, chromatin regulators and histone modifying enzymes with opposite enzymatic activities are coenriched in undifferentiated cells in testis, suggesting that these cells may possess dynamic chromatin architecture. Finally, our data revealed many new features of the Drosophila gonadal transcriptomes, and will lead to a more comprehensive understanding of how differential gene expression and splicing regulate gametogenesis in Drosophila. Our data provided a foundation for the systematic study of gene expression and alternative splicing in many interesting areas of germ cell biology in Drosophila, such as the molecular basis for sexual dimorphism and the regulation of the proliferation vs terminal differentiation programs in germline stem cell lineages. The GEO accession number for the raw and analyzed RNA-seq data is GSE16960.

Dataset Information

Spatio-temporal and dynamic regulation of neurofascin alternative splicing in mouse cerebellar neurons.

Publications

Spatio-temporal and dynamic regulation of neurofascin alternative splicing in mouse cerebellar neurons.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets