Similar Datasets
Project description:The hippocampus plays major roles in learning and memory, and its formation requires precise coordination of patterning, cell proliferation, differentiation, and migration. Here we removed the chromatin-association capability of KDM2B in the progenitors of developing dorsal telencephalon (Kdm2b∆CxxC) to discover that Kdm2b∆CxxC hippocampus, particularly the dentate gyrus, became drastically smaller with disorganized cellular components and structure. Kdm2b∆CxxC mice display prominent defects in spatial memory, motor learning and fear conditioning, resembling patients with KDM2B mutations. The migration and differentiation of neural progenitor cells is greatly impeded in the developing Kdm2b∆CxxC hippocampus. Mechanism studies reveal that Wnt signaling genes in developing Kdm2b∆CxxC hippocampi are de-repressed due to reduced enrichment of repressive histone marks by polycomb repressive complexes. Activating the Wnt signaling disturbs hippocampal neurogenesis, recapitulating the effect of KDM2B loss. Together, we unveil a previously unappreciated gene repressive program mediated by KDM2B that controls progressive fate specifications and cell migration, hence morphogenesis of the hippocampus.
| S-EPMC10576813 | biostudies-literature
Project 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-∆CxxC) to surprisingly discover that the size of Kdm2bEmx1-∆CxxC hippocampus, particularly the dentate gyrus, became drastically smaller with disorganized cellular components and structure. Kdm2bEmx1-∆CxxC mice displayed prominent defects in spatial memory, motor learning and fear conditioning. The differentiation path of the developing Kdm2bEmx1-∆CxxC 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.
2023-09-25 | GSE222464 | GEO
Project 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-∆CxxC) to surprisingly discover that the size of Kdm2bEmx1-∆CxxC hippocampus, particularly the dentate gyrus, became drastically smaller with disorganized cellular components and structure. Kdm2bEmx1-∆CxxC mice displayed prominent defects in spatial memory, motor learning and fear conditioning. The differentiation path of the developing Kdm2bEmx1-∆CxxC 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.
2023-09-25 | GSE222463 | GEO
Project 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-∆CxxC) to surprisingly discover that the size of Kdm2bEmx1-∆CxxC hippocampus, particularly the dentate gyrus, became drastically smaller with disorganized cellular components and structure. Kdm2bEmx1-∆CxxC mice displayed prominent defects in spatial memory, motor learning and fear conditioning. The differentiation path of the developing Kdm2bEmx1-∆CxxC 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.
2023-09-25 | GSE222462 | GEO
Project description:KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors
| PRJNA922143 | ENA
Project description:KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors (ATAC-Seq)
| PRJNA922153 | ENA
Project description:KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors (RNA-Seq)
| PRJNA922155 | ENA
Project description:KDM2B regulates hippocampal morphogenesis by transcriptionally silencing Wnt signaling in neural progenitors (ChIP-Seq)
| PRJNA922154 | ENA
Project description:Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix(-/-) mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix(-/-) mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix(-/-) mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure.
| S-EPMC3862270 | biostudies-literature
Project description:Cortical intermediate progenitors (IPs) comprise a secondary neuronal progenitor pool that arises from radial glia (RG). IPs are essential for generating the correct number of cortical neurons, but the factors that regulate the expansion and differentiation of IPs in the embryonic cortex are essentially unknown. In this study, we show that the Wnt-?-catenin pathway (canonical Wnt pathway) regulates IP differentiation into neurons. Upregulation of Wnt-?-catenin signaling by overexpression of Wnt3a in the neocortex induced early differentiation of IPs into neurons and the accumulation of these newly born neurons at the subventricular zone/intermediate zone border. Long-term overexpression of Wnt3a led to cortical dysplasia associated with the formation of large neuronal heterotopias. Conversely, downregulation of Wnt-?-catenin signaling with Dkk1 during mid and late stages of neurogenesis inhibited neuronal production. Consistent with previous reports, we show that Wnt-?-catenin signaling also promotes RG self-renewal. Thus, our findings show differential effects of the Wnt-?-catenin pathway on distinct groups of cortical neuronal progenitors: RG self-renewal and IP differentiation. Moreover, our findings suggest that dysregulation of Wnt signaling can lead to developmental defects similar to human cortical malformation disorders.
| S-EPMC3040956 | biostudies-literature