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

Rebecca Favaro, Menella Valotta, Anna L M Ferri, Elisa Latorre, Jessica Mariani, Claudio Giachino, Cesare Lancini, Valentina Tosetti, Sergio Ottolenghi, Verdon Taylor, Silvia K. Nicolis

Research output: Contribution to journalArticle

302 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1248-1256
Number of pages9
JournalNature Neuroscience
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 2009

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Hedgehogs
Neural Stem Cells
Maintenance
Neurogenesis
Hippocampus
Brain
Chromatin Immunoprecipitation
Dentate Gyrus
Conditioned Culture Medium
Transcription Factors
Parturition
Pharmacology
Mutation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Favaro, R., Valotta, M., Ferri, A. L. M., Latorre, E., Mariani, J., Giachino, C., ... Nicolis, S. K. (2009). Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nature Neuroscience, 12(10), 1248-1256. https://doi.org/10.1038/nn.2397

Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. / Favaro, Rebecca; Valotta, Menella; Ferri, Anna L M; Latorre, Elisa; Mariani, Jessica; Giachino, Claudio; Lancini, Cesare; Tosetti, Valentina; Ottolenghi, Sergio; Taylor, Verdon; Nicolis, Silvia K.

In: Nature Neuroscience, Vol. 12, No. 10, 10.2009, p. 1248-1256.

Research output: Contribution to journalArticle

Favaro, R, Valotta, M, Ferri, ALM, Latorre, E, Mariani, J, Giachino, C, Lancini, C, Tosetti, V, Ottolenghi, S, Taylor, V & Nicolis, SK 2009, 'Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh', Nature Neuroscience, vol. 12, no. 10, pp. 1248-1256. https://doi.org/10.1038/nn.2397
Favaro R, Valotta M, Ferri ALM, Latorre E, Mariani J, Giachino C et al. Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nature Neuroscience. 2009 Oct;12(10):1248-1256. https://doi.org/10.1038/nn.2397
Favaro, Rebecca ; Valotta, Menella ; Ferri, Anna L M ; Latorre, Elisa ; Mariani, Jessica ; Giachino, Claudio ; Lancini, Cesare ; Tosetti, Valentina ; Ottolenghi, Sergio ; Taylor, Verdon ; Nicolis, Silvia K. / Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. In: Nature Neuroscience. 2009 ; Vol. 12, No. 10. pp. 1248-1256.
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