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

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

doi:10.1038/nn.2397

Cited by 454 publications

(551 citation statements)

References 46 publications

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“…Further, we did not detect (Figure 3c) 5 . Further, we used a Cre-reporter allele (R26R::LacZ) to monitor the recombined cells in vivo 34 .…”

Section: Sox2 Is Expressed In Murine Melanoma But Not Critical For Sumentioning

confidence: 58%

“…It controls pluripotency in embryonic stem cells and is one of the four originally described factors required for reprogramming of differentiated cells into induced pluripotent stem cells 3,4 . Sox2 has been extensively studied in the central nervous system, where it regulates maintenance of stem and progenitor cells [5][6][7][8] . Likewise, in adult mouse tissue, Sox2 marks epithelial stem cells in various tissues of endodermal and ectodermal origin and is required for their homeostasis 9 .…”

Section: Introductionmentioning

confidence: 99%

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Sox2 is dispensable for primary melanoma and metastasis formation

et al. 2017

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Tumor initiation and metastasis formation in many cancers have been associated with emergence of a gene expression program normally active in embryonic or organ-specific stem cells. In particular, the stem cell transcription factor Sox2 is not only expressed in a variety of tumors, but is also required for their formation. Melanoma, the most aggressive skin tumor, derives from melanocytes that during development originate from neural crest stem cells. While neural crest stem cells do not express Sox2, expression of this transcription factor has been reported in melanoma. However, the role of Sox2 in melanoma is controversial. To study the requirement of Sox2 for melanoma formation, we therefore performed CRISPR-Cas9-mediated gene inactivation in human melanoma cells. In addition, we conditionally inactivated Sox2 in a genetically engineered mouse model, in which melanoma spontaneously develops in the context of an intact stroma and immune system. Surprisingly, in both models, loss of Sox2 did neither affect melanoma initiation, nor growth, nor metastasis formation. The lack of a tumorigenic role of Sox2 in melanoma might reflect a distinct stem cell program active in neural crest stem cells and during melanoma formation.

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“…Further, we did not detect (Figure 3c) 5 . Further, we used a Cre-reporter allele (R26R::LacZ) to monitor the recombined cells in vivo 34 .…”

Section: Sox2 Is Expressed In Murine Melanoma But Not Critical For Sumentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Sox2 is dispensable for primary melanoma and metastasis formation

et al. 2017

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“…The generation of Sox2 bgeo and Sox2 loxP mice has been previously described in [4,20], respectively. TNAP Cre mice were a gift from Dr. D. O'Carroll (EMBL, Monterotondo, Italy).…”

Section: Micementioning

confidence: 99%

Essential Role of Sox2 for the Establishment and Maintenance of the Germ Cell Line

et al. 2013

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Sox2 is a pluripotency-conferring gene expressed in primordial germ cells (PGCs) and postnatal oocytes, but the role it plays during germ cell development and early embryogenesis is unknown. Since Sox2 ablation causes early embryonic lethality shortly after blastocyst implantation, we generated mice bearing Sox2-conditional deletion in germ cells at different stages of their development through the Cre/loxP recombination system. Embryos lacking Sox2 in PGCs show a dramatic decrease of germ cell numbers at the time of their specification. At later stages, we found that Sox2 is strictly required for PGC proliferation. On the contrary, Sox2 deletion in meiotic oocytes does not impair postnatal oogenesis and early embryogenesis, indicating that it is not essential for oocyte maturation or for zygotic development. We also show that Sox2 regulates Kit expression in PGCs and binds to discrete transcriptional regulatory sequences of this gene, which is known to be important for PGCs survival and proliferation. Sox2 also stimulates the expression of Zfp148, which is required for normal development of fetal germ cells, and Rif1, a potential regulator of PGC pluripotency.

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“…Amplification in the lineage is thought to occur through multiple symmetric divisions of IPs, primarily at the type-2a stage 5,42,43 . To shed light on the neurogenic process, several transgenic mouse lines have been used to lineage trace NSCs in a controlled manner 10,[13][14][15][16][17][18][44][45][46][47] . However, the expression of most transgenes is not restricted in the SGZ to NSCs, resulting in labeling of more differentiated cell types 5,20 .…”

Section: Hes5creermentioning

confidence: 99%

Homeostatic neurogenesis in the adult hippocampus does not involve amplification of Ascl1high intermediate progenitors

et al. 2012

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neural stem/progenitor cells generate neurons in the adult hippocampus. neural stem cells produce transient intermediate progenitors (type-2 cells), which generate neuroblasts (type-3 cells) that exit the cell cycle, and differentiate into neurons. The precise dynamics of neuron production from the neural stem cells remains controversial. Here we lineage trace notchdependent neural stem cells in the dentate gyrus and show that over 7-21 days, the progeny of the neural stem cells progress through an Ascl1 high intermediate stage (type-2a) to neuroblasts. However, contrary to predictions, this Ascl1 high population is not an amplifying intermediate, but it differentiates into mitotic Tbr2 + early neuroblasts, which in turn expand the lineage. After 100 days, the majority of the neural stem cell progeny are neuroblasts or postmitotic neurons. Hence, the neural stem cells require many weeks to generate differentiated neurons. on the basis of this temporal delay in differentiation and population expansion, we propose that the neural stem cell and early neuroblast divisions drive dentate gyrus neurogenesis and not the amplification of type-2a intermediate progenitors as was previously thought.

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

Cited by 454 publications

References 46 publications

Sox2 is dispensable for primary melanoma and metastasis formation

Sox2 is dispensable for primary melanoma and metastasis formation

Essential Role of Sox2 for the Establishment and Maintenance of the Germ Cell Line

Homeostatic neurogenesis in the adult hippocampus does not involve amplification of Ascl1high intermediate progenitors

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