An early Sox2-dependent gene expression programme required for hippocampal dentate gyrus development
| Autor: | Pietro Berico, Simone Meneghini, Sara Mercurio, Silvia K. Nicolis, Linda Serra, Andrea Becchetti, Chiara Alberti, Jessica Bertolini |
|---|---|
| Přispěvatelé: | Mercurio, S, Alberti, C, Serra, L, Meneghini, S, Berico, P, Bertolini, J, Becchetti, A, Nicolis, S |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Receptors
CXCR4 Immunology Sox2 Hippocampus Action Potentials Nerve Tissue Proteins Biology Hippocampal formation General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Mice 0302 clinical medicine SOX2 Zinc Finger Protein Gli3 transcription factors Cell Line Tumor Wnt3A Protein Intellectual disability Gene expression medicine Animals lcsh:QH301-705.5 Transcription factor transcription factor 030304 developmental biology mouse genetic model Regulation of gene expression Neurons 0303 health sciences mouse genetic models General Neuroscience Dentate gyrus SOXB1 Transcription Factors fungi Gene Expression Regulation Developmental Tumor Protein p73 medicine.disease Mice Inbred C57BL lcsh:Biology (General) embryonic structures Dentate Gyrus Sox T-Box Domain Proteins gene regulation Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Open Biology, Vol 11, Iss 2 (2021) |
| Popis: | The hippocampus is a brain area central for cognition. Mutations in the human SOX2 transcription factor cause neurodevelopmental defects, leading to intellectual disability and seizures, together with hippocampal dysplasia. We generated an allelic series of Sox2 conditional mutations in mouse, deleting Sox2 at different developmental stages. Late Sox2 deletion (from E11.5, via Nestin-Cre) affects only postnatal hippocampal development; earlier deletion (from E10.5, Emx1-Cre) significantly reduces the dentate gyrus (DG), and the earliest deletion (from E9.5, FoxG1-Cre) causes drastic abnormalities, with almost complete absence of the DG. We identify a set of functionally interconnected genes (Gli3, Wnt3a, Cxcr4, p73 and Tbr2), known to play essential roles in hippocampal embryogenesis, which are downregulated in early Sox2 mutants, and (Gli3 and Cxcr4) directly controlled by SOX2; their downregulation provides plausible molecular mechanisms contributing to the defect. Electrophysiological studies of the Emx1-Cre mouse model reveal altered excitatory transmission in CA1 and CA3 regions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|