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.
Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh / R. Favaro, M. Valotta, A.L.M. Ferri, E. Latorre, J. Mariani, C. Giachino, C. Lancini, V. Tosetti, S. Ottolenghi, V. Taylor, S.K. Nicolis. - In: NATURE NEUROSCIENCE. - ISSN 1097-6256. - 12:10(2009 Oct), pp. 1248-1256.
|Titolo:||Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh|
|Parole Chiave:||hippocampus ; age factors ; animals ; animals, newborn ; bromodeoxyuridine ; cell differentiation ; cell survival ; cells, cultured ; chromatin immunoprecipitation ; culture media, conditioned ; DNA nucleotidyltransferases ; electrophoretic mobility shift assay ; embryo, mammalian ; embryonic stem cells ; enzyme inhibitors ; female ; gene expression regulation, developmental ; green fluorescent proteins ; hedgehog proteins ; in situ Nick-end labeling ; intercellular signaling peptides and proteins ; intermediate filament proteins ; mice ; mice, inbred C57BL ; mice, transgenic ; mutation ; nerve tissue proteins ; nestin ; neurogenesis ; neurons ; RNA, messenger ; SOXB1 transcription factors ; signal transduction ; Wnt proteins ; Wnt3 protein ; Wnt3A protein|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
Settore BIO/18 - Genetica
|Data di pubblicazione:||ott-2009|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/nn.2397|
|Appare nelle tipologie:||01 - Articolo su periodico|