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PMID:17576749

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Citation

Appolloni, I, Calzolari, F, Corte, G, Perris, R and Malatesta, P (2008) Six3 controls the neural progenitor status in the murine CNS. Cereb. Cortex 18:553-62

Abstract

Six3, a homeodomain-containing transcriptional regulator belonging to the Six/so family, shows a defined spatiotemporal expression pattern in the developing murine telencephalon, suggesting that it may control the development of specific subsets of neural progenitors. We find that retrovirus-mediated misexpression of Six3 causes clonal expansion of isolated cortical progenitor cells by shortening their cell cycle and by prolonging their amplification period, while maintaining them in an immature precursor state. Our results show that the observed effects exerted by Six3 overexpression in mammalian brain depend strictly on the integrity of its DNA-binding domain, suggesting that Six3 action likely relies exclusively on its transcriptional activity. In vivo upregulation of Six3 expression in single progenitor cells of the embryonic telencephalon keeps them in an undifferentiated state. Our observations point to a role of Six3 in the control of the subtle equilibrium between proliferation and differentiation of defined precursor populations during mammalian neurogenesis.

Links

PubMed Online version:10.1093/cercor/bhm092

Keywords

Animals; Base Sequence; Cells, Cultured; DNA-Binding Proteins/biosynthesis; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Eye Proteins/biosynthesis; Eye Proteins/genetics; Eye Proteins/metabolism; Eye Proteins/physiology; Homeodomain Proteins/biosynthesis; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Homeodomain Proteins/physiology; Humans; Mice; Molecular Sequence Data; NIH 3T3 Cells; Nerve Tissue Proteins/biosynthesis; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Nerve Tissue Proteins/physiology; Neurons/cytology; Neurons/metabolism; Neurons/physiology; Stem Cells/cytology; Stem Cells/metabolism; Stem Cells/physiology; Telencephalon/cytology; Telencephalon/metabolism; Telencephalon/physiology; Up-Regulation/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:SIX3

involved_in

GO:0045665: negative regulation of neuron differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SIX3

involved_in

GO:2000177: regulation of neural precursor cell proliferation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SIX3

involved_in

GO:1901987: regulation of cell cycle phase transition

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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