Review: adult neurogenesis contributes to hippocampal plasticity
Tomohisha Toda,
Fred H. Gage
Cell and Tissue Research
373
693-709
(2017)
| Journal
Adult hippocampal neurogenesis is the process by which new functional neurons are added to the adult dentate gyrus of the hippocampus. Animal studies have shown that the degree of adult hippocampal neurogenesis is regulated by local environmental cues as well as neural network activities. Furthermore, accumulating evidence has suggested that adult hippocampal neurogenesis plays prominent roles in hippocampus-dependent brain functions. In this review, we summarize the mechanisms underlying the regulation of adult hippocampal neurogenesis at various developmental stages and propose how adult-born neurons contribute to structural and functional hippocampal plasticity.
Nup153 Interacts with Sox2 to Enable Bimodal Gene Regulation and Maintenance of Neural Progenitor Cells
Tomohisha Toda,
Jonathan Y. Hsu,
Sara B. Linker,
Lauren Hu,
Simon T. Schafer,
Jerome Mertens,
Filipe V. Jacinto,
Martin W. Hetzer,
Fred H. Gage
Neural progenitor cells (NeuPCs) possess a unique nuclear architecture that changes during differentiation. Nucleoporins are linked with cell-type-specific gene regulation, coupling physical changes in nuclear structure to transcriptional output; but, whether and how they coordinate with key fate-determining transcription factors is unclear. Here we show that the nucleoporin Nup153 interacts with Sox2 in adult NeuPCs, where it is indispensable for their maintenance and controls neuronal differentiation. Genome-wide analyses show that Nup153 and Sox2 bind and co-regulate hundreds of genes. Binding of Nup153 to gene promoters or transcriptional end sites correlates with increased or decreased gene expression, respectively, and inhibiting Nup153 expression alters open chromatin configurations at its target genes, disrupts genomic localization of Sox2, and promotes differentiation in vitro and a gliogenic fate switch in vivo. Together, these findings reveal that nuclear structural proteins may exert bimodal transcriptional effects to control cell fate.
Contact
Research Group Tomohisa Toda
Max-Planck-Zentrum für Physik und Medizin Kussmaulallee 2 91054 Erlangen, Germany
