Neural stem cells (NSCs) are controlled by diffusible factors. The transcription factor Sox2 is expressed by NSCs and Sox2 mutations in humans cause defects in the brain and, in particular, in the hippocampus. We deleted Sox2 in the mouse embryonic brain. At birth, the mice showed minor brain defects; shortly afterwards, however, NSCs and neurogenesis were completely lost in the hippocampus, leading to dentate gyrus hypoplasia. Deletion of Sox2 in adult mice also caused hippocampal neurogenesis loss. The hippocampal developmental defect resembles that caused by late sonic hedgehog (Shh) loss. In mutant mice, Shh and Wnt3a were absent from the hippocampal primordium. A SHH pharmacological agonist partially rescued the hippocampal defect. Chromatin immunoprecipitation identified Shh as a Sox2 target. Sox2-deleted NSCs did not express Shh in vitro and were rapidly lost. Their replication was partially rescued by the addition of SHH and was almost fully rescued by conditioned medium from normal cells. Thus, NSCs control their status, at least partly, through Sox2-dependent autocrine mechanisms.

Favaro, R., Valotta, M., Ferri, A., Latorre, E., Mariani, J., Giachino, C., et al. (2009). Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. NATURE NEUROSCIENCE, 12(10), 1248-1256 [10.1038/nn.2397].

Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh

FERRI, ANNA LUCIA MARIA;MARIANI, JESSICA;LANCINI, CESARE;OTTOLENGHI, SERGIO;NICOLIS, SILVIA KIRSTEN
2009

Abstract

Neural stem cells (NSCs) are controlled by diffusible factors. The transcription factor Sox2 is expressed by NSCs and Sox2 mutations in humans cause defects in the brain and, in particular, in the hippocampus. We deleted Sox2 in the mouse embryonic brain. At birth, the mice showed minor brain defects; shortly afterwards, however, NSCs and neurogenesis were completely lost in the hippocampus, leading to dentate gyrus hypoplasia. Deletion of Sox2 in adult mice also caused hippocampal neurogenesis loss. The hippocampal developmental defect resembles that caused by late sonic hedgehog (Shh) loss. In mutant mice, Shh and Wnt3a were absent from the hippocampal primordium. A SHH pharmacological agonist partially rescued the hippocampal defect. Chromatin immunoprecipitation identified Shh as a Sox2 target. Sox2-deleted NSCs did not express Shh in vitro and were rapidly lost. Their replication was partially rescued by the addition of SHH and was almost fully rescued by conditioned medium from normal cells. Thus, NSCs control their status, at least partly, through Sox2-dependent autocrine mechanisms.
Articolo in rivista - Articolo scientifico
Neurogenesis; Electrophoretic Mobility Shift Assay; Hedgehog Proteins; Mutation; Embryo, Mammalian; DNA Nucleotidyltransferases; Embryonic Stem Cells; Age Factors; Animals, Newborn; Enzyme Inhibitors; Cell Differentiation; Gene Expression Regulation, Developmental; Mice; Nerve Tissue Proteins; Wnt Proteins; Intercellular Signaling Peptides and Proteins; Chromatin Immunoprecipitation; Hippocampus; Cells, Cultured; Bromodeoxyuridine; Female; Culture Media, Conditioned; SOXB1 Transcription Factors; Green Fluorescent Proteins; Animals; Mice, Transgenic; Cell Survival; RNA, Messenger; Signal Transduction; Neurons; Intermediate Filament Proteins; Mice, Inbred C57BL; In Situ Nick-End Labeling
English
2009
12
10
1248
1256
none
Favaro, R., Valotta, M., Ferri, A., Latorre, E., Mariani, J., Giachino, C., et al. (2009). Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. NATURE NEUROSCIENCE, 12(10), 1248-1256 [10.1038/nn.2397].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/14486
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