Abstract
New neurons continuously arise from neural progenitor cells in the dentate gyrus of the adult hippocampus to support ongoing learning and memory formation. To generate functional adult-born neurons, neural progenitor cells proliferate to expand the precursor cell pool and differentiate into neurons. Newly generated cells then undergo postmitotic maturation to migrate to their final destination and develop elaborate dendritic branching, which allows them to receive input signals. Little is known about factors that regulate neuronal differentiation, migration, and dendrite maturation during adult hippocampal neurogenesis. Here, we show that the transcriptional repressor protein capicua (CIC) exhibits dynamic expression in the adult dentate gyrus. Conditional deletion of Cic from the mouse dentate gyrus compromises the adult neural progenitor cell pool without altering their proliferative potential. We further demonstrate that the loss of Cic impedes neuronal lineage development and disrupts dendritic arborization and migration of adult-born neurons. Our study uncovers a previously unrecognized role of CIC in neurogenesis of the adult dentate gyrus.
Highlights
New neurons continuously arise from neural progenitor cells in the dentate gyrus of the adult hippocampus to support ongoing learning and memory formation
Quiescent radial glia-like (RGL) cells reside in the subgranular zone; upon activation, radial glial-like (RGL) cells differentiate into rapidly amplifying type 2a/b intermediate progenitor cells (IPCs)[2]
We observed nuclear CIC staining in the subgranular zone (SGZ) among neural progenitors (SOX2+ RGL cells and type 2a IPCs) (Fig. 1D). DCX+ neuroblasts/immature neurons showed a minimal level of CIC (Fig. 1E)
Summary
New neurons continuously arise from neural progenitor cells in the dentate gyrus of the adult hippocampus to support ongoing learning and memory formation. Quiescent radial glial-like (RGL) neural progenitor cells, which reside in the subgranular zone (SGZ) of the hippocampal dentate gyrus, develop into mature granule neurons through four phases: a progenitor cell phase, an early survival phase, a postmitotic maturation phase, and a late survival/maturation phase[2]. This entire process takes about 6–8 weeks and encompasses six developmental milestones which can be identified based on molecular markers and cell morphology (Fig. 1A). Statistical analyses were performed with one-way ANOVA with Tukey’s post hoc test (in G) or two-tailed Student’s t-test (H, I). ****P < 0.0001
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