Abstract
Pax6 is a key regulator in the neuronal fate determination as well as the proliferation of neural stem cells, but the mechanisms are still unknown. Our study shows that Pax6 regulate the proliferation of neural progenitor cells of cortical subventricular zone, through direct modulation of the Sox2 expression during the late developmental stage in mice. We found a dramatic decrease in the number of Sox2+ neural progenitor cells in the subventricular zone of E18.5 Pax6(-/-) mice. We confirmed that Pax6 could bind to the Sox2 promoter by chromatin immunoprecipitation assay and activate Sox2 expression by a luciferase reporter gene assay. Moreover, neural progenitors isolated from the Pax6(-/-) embryos showed a decreased neurosphere formation as well as proliferation.
MeSH terms
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Animals
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Biological Assay
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Body Patterning / genetics
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Brain / cytology
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Brain / embryology*
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Brain / metabolism*
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Cell Differentiation / genetics
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Cell Proliferation
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Eye Proteins / genetics
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Eye Proteins / physiology*
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Gene Expression Regulation, Developmental / genetics
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Genes, Reporter / genetics
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HMGB Proteins / genetics
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HMGB Proteins / metabolism*
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Homeodomain Proteins / genetics
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Homeodomain Proteins / physiology*
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Luciferases / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neurons / metabolism*
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PAX6 Transcription Factor
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Paired Box Transcription Factors / genetics
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Paired Box Transcription Factors / physiology*
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Promoter Regions, Genetic / genetics
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Protein Binding / genetics
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Repressor Proteins / genetics
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Repressor Proteins / physiology*
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SOXB1 Transcription Factors
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Spheroids, Cellular
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Stem Cells / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation / genetics
Substances
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DNA-Binding Proteins
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Eye Proteins
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HMGB Proteins
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Homeodomain Proteins
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PAX6 Transcription Factor
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Paired Box Transcription Factors
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Pax6 protein, mouse
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Repressor Proteins
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SOXB1 Transcription Factors
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Sox2 protein, mouse
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Transcription Factors
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Luciferases