RT Journal Article
SR Electronic
T1 An early Sox2-dependent gene expression program required for hippocampal dentate gyrus development
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.16.252684
DO 10.1101/2020.08.16.252684
A1 Sara Mercurio
A1 Chiara Alberti
A1 Linda Serra
A1 Simone Meneghini
A1 Jessica Bertolini
A1 Pietro Berico
A1 Andrea Becchetti
A1 Silvia K. Nicolis
YR 2020
UL http://biorxiv.org/content/early/2020/08/16/2020.08.16.252684.abstract
AB 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, and the earliest deletion (from E9.5, FoxG1-Cre) causes drastic abnormalities, with almost complete absence of the dentate gyrus. 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 Emx1Cre mouse model reveal altered excitatory transmission in CA1 and CA3 regions.Competing Interest StatementThe authors have declared no competing interest.