Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA292566 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in FoxO6+/- and FoxO6-/- mice, showing migrating neurons halted in the intermediate zone. Using a FoxO6-directed siRNA approach, we substantiate the requirement of FoxO6 for a correct radial migration in the developing neocortex. Subsequent genome-wide transcriptome analysis reveals altered expression of genes involved in cell adhesion, axon guidance, and gliogenesis upon silencing of FoxO6 We then show that FoxO6 binds to DAF-16-binding elements in the Plexin A4 (Plxna4) promoter region and affects Plxna4 expression. Finally, ectopic Plxna4 expression restores radial migration in FoxO6+/- and siRNA-mediated knockdown models. In conclusion, the presented data provide insights into the molecular mechanisms whereby transcriptional programs drive cortical development.
2016-11-11 | GSE71954 | GEO
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:Nonsense-mediated mRNA decay (NMD) is associated with various neurodevelopmental disorders. Here, we demonstrate that NMD, mediated by UPF2, previously not linked to cortical organization, is indispensable for neuronal migration and cortical lamination. Conditional deletion of Upf2 in radial glial cells delays neuronal migration and disrupts cortical lamination. Trp53 knockout rescues microcephaly from Upf2 deficiency but cannot rescue lamination defects, showing that UPF2’s role in neuronal migration is uncoupled from its regulation of cell cycle and independent of p53. UPF2 deficiency downregulates key neuronal migration genes in the Reelin signaling pathway and microtubule assembly (e.g., Dab1, Lrp8, Tubb2b, Tuba1a), partly through upregulation of the transcriptional repressor Ino80. Additionally, NMD inhibition causes widespread upregulation of ciliary genes. Ectopic expression of Foxj1, a master regulator of ciliary genes and NMD target, impedes neuronal migration, mimicking the Upf2 knockout phenotype. Therefore, NMD is a central post-transcriptional mechanism that coordinates migration and ciliary gene networks crucial for cortical structure development, providing insight into how NMD dysfunction contributes to neurodevelopmental disorders.
2025-12-20 | GSE295221 | GEO
Project description:Nonsense-mediated mRNA decay (NMD) is associated with various neurodevelopmental disorders. Here, we demonstrate that NMD, mediated by UPF2, previously not linked to cortical organization, is indispensable for neuronal migration and cortical lamination. Conditional deletion of Upf2 in radial glial cells delays neuronal migration and disrupts cortical lamination. Trp53 knockout rescues microcephaly from Upf2 deficiency but cannot rescue lamination defects, showing that UPF2’s role in neuronal migration is uncoupled from its regulation of cell cycle and independent of p53. UPF2 deficiency downregulates key neuronal migration genes in the Reelin signaling pathway and microtubule assembly (e.g., Dab1, Lrp8, Tubb2b, Tuba1a), partly through upregulation of the transcriptional repressor Ino80. Additionally, NMD inhibition causes widespread upregulation of ciliary genes. Ectopic expression of Foxj1, a master regulator of ciliary genes and NMD target, impedes neuronal migration, mimicking the Upf2 knockout phenotype. Therefore, NMD is a central post-transcriptional mechanism that coordinates migration and ciliary gene networks crucial for cortical structure development, providing insight into how NMD dysfunction contributes to neurodevelopmental disorders.
2025-12-20 | GSE295222 | GEO
Project description:During mammalian neural development, precise regulation of gene expression in neural progenitor cells (NPCs) is critical for proper formation of the cortex. Although the regulatory mechanism of the transcription factor Sox2 has been extensively examined, the role of its distal regulatory elements remains poorly understood. Here, we identified a Sox2 regulatory region located 42 kb downstream of the Sox2 TSS (SRR42) that exhibits hallmark features of an active regulatory element, including open chromatin, histone modifications, and bidirectional transcription of enhancer RNAs (eRNAs). Using transgenic reporter mice, we found that SRR42 is specifically active in NPCs in the developing mouse brain. CRISPR-Cas9-mediated deletion of SRR42 in mice together with single-cell multiome analysis further revealed the involvement of SRR42 regions in the regulation of neuronal migration and cortical lamination. Knockdown of SRR42 eRNAs in vivo impaired neuronal migration, indicating that these eRNAs regulate neuronal development. Our study demonstrated that SRR42 functions through an eRNA-mediated mechanism to precisely control neuronal positioning during mammalian cortical development, which is not associated with Sox2 transactivation. These findings provide new insights into the epigenetic regulation of cortical formation and may help understand neurodevelopmental disorders.
2026-07-23 | GSE297056 | GEO
Project description:During mammalian neural development, precise regulation of gene expression in neural progenitor cells (NPCs) is critical for proper formation of the cortex. Although the regulatory mechanism of the transcription factor Sox2 has been extensively examined, the role of its distal regulatory elements remains poorly understood. Here, we identified a Sox2 regulatory region located 42 kb downstream of the Sox2 TSS (SRR42) that exhibits hallmark features of an active regulatory element, including open chromatin, histone modifications, and bidirectional transcription of enhancer RNAs (eRNAs). Using transgenic reporter mice, we found that SRR42 is specifically active in NPCs in the developing mouse brain. CRISPR-Cas9-mediated deletion of SRR42 in mice together with single-cell multiome analysis further revealed the involvement of SRR42 regions in the regulation of neuronal migration and cortical lamination. Knockdown of SRR42 eRNAs in vivo impaired neuronal migration, indicating that these eRNAs regulate neuronal development. Our study demonstrated that SRR42 functions through an eRNA-mediated mechanism to precisely control neuronal positioning during mammalian cortical development, which is not associated with Sox2 transactivation. These findings provide new insights into the epigenetic regulation of cortical formation and may help understand neurodevelopmental disorders.
2026-07-23 | GSE282390 | GEO
Project description:During mammalian neural development, precise regulation of gene expression in neural progenitor cells (NPCs) is critical for proper formation of the cortex. Although the regulatory mechanism of the transcription factor Sox2 has been extensively examined, the role of its distal regulatory elements remains poorly understood. Here, we identified a Sox2 regulatory region located 42 kb downstream of the Sox2 TSS (SRR42) that exhibits hallmark features of an active regulatory element, including open chromatin, histone modifications, and bidirectional transcription of enhancer RNAs (eRNAs). Using transgenic reporter mice, we found that SRR42 is specifically active in NPCs in the developing mouse brain. CRISPR-Cas9-mediated deletion of SRR42 in mice together with single-cell multiome analysis further revealed the involvement of SRR42 regions in the regulation of neuronal migration and cortical lamination. Knockdown of SRR42 eRNAs in vivo impaired neuronal migration, indicating that these eRNAs regulate neuronal development. Our study demonstrated that SRR42 functions through an eRNA-mediated mechanism to precisely control neuronal positioning during mammalian cortical development, which is not associated with Sox2 transactivation. These findings provide new insights into the epigenetic regulation of cortical formation and may help understand neurodevelopmental disorders.
2026-07-23 | GSE296925 | GEO
Project description:Completion of neuronal migration is critical for brain development. Kif21b is a plus-end directed kinesin motor protein that promotes intracellular transport and controls microtubule dynamics in neurons. Here we report a physiological function of Kif21b during radial migration of projection neurons in the mouse developing cortex. In vivo analysis in mouse and live imaging on cultured slices demonstrate that Kif21b regulates the radial glia-guided locomotion of new-born neurons independently of its motility on microtubules. Unexpectedly we show that Kif21b directly binds and regulates the actin cytoskeleton both in vitro and in vivo in migratory neurons. We establish that Kif21b-mediated regulation of actin cytoskeleton dynamics influences branching and nucleokinesis during neuronal locomotion. Altogether, our results reveal atypical roles of Kif21b on the actin cytoskeleton during migration of cortical projection neurons
2023-07-04 | PXD042855 | Pride
Project description: Not available
| S-EPMC11335981 | biostudies-literature