| Experiment Id | GSE222464 | Name | KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors (RNA-Seq) |
| Experiment Type | RNA-Seq | Study Type | WT vs. Mutant |
| Source | GEO | Curation Date | 2023-10-26 |
| description | The hippocampus plays major roles in learning and memory. Similar to other parts of the brain, the development of hippocampus requires precise coordination of patterning, cell proliferation, differentiation, and migration, with both cell-intrinsic and extrinsic mechanisms involved. Here we genetically removed the chromatin-association capability of KDM2B - a key component of the variant Polycomb repressive complex 1 (PRC1) - in the developing dorsal telencephalon (Kdm2bEmx1-deltaCxxC) to surprisingly discover that the size of Kdm2bEmx1-deltaCxxC hippocampus, particularly the dentate gyrus, became drastically smaller with disorganized cellular components and structure. Kdm2bEmx1-deltaCxxC mice displayed prominent defects in spatial memory, motor learning and fear conditioning. The differentiation path of the developing Kdm2bEmx1-deltaCxxC hippocampus was greatly delayed, with significant amount of TBR2-expressing intermediate progenitors being stuck along the migratory path. Transcriptome and chromatin immunoprecipitation studies of neonatal hippocampi and their progenitors indicated that genes implicated in stemness maintenance, especially components of canonical Wnt signaling, could not be properly silenced by PRC1 and PRC2. Activating Wnt signaling disturbed hippocampal neurogenesis, recapitulating the effect of KDM2B loss. Together, we unveiled a previously unappreciated gene repressive program mediated by KDM2B that controls progressive fate specifications and cell migration, hence morphogenesis of hippocampus during development. Comparative gene expression profiling analysis of RNA-seq data for P0 mouse cortex of control and Kdm2b-cKO(Emx1-deltaCxxC), and P0 mouse hippocampi of control and Rnf2-cKO. |
