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Status |
Public on Jan 31, 2013 |
Title |
E12.5 Murine lateral cortical progenitor cells: Pax6sey/sey vs. Pax6+/+ |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
The mechanisms by which the early spatiotemporal expression patterns of transcription factors such as Pax6 regulate the region-specific proliferation rates of neural progenitors are poorly understood. Pax6 is expressed in a gradient across the developing cortex and is essential for normal corticogenesis. We found that constitutive or conditional loss of Pax6 increases cortical progenitor proliferation by amounts that vary regionally with normal Pax6 levels. We compared the gene expression profiles of equivalent Pax6-expressing progenitors isolated from Pax6+/+ and Pax6-/- cortices and identified many negatively-regulated cell cycle genes including those encoding Cyclins and Cdks. Biochemical assays indicated that Pax6 directly represses Cdk6 expression. Cyclin/Cdk repression inhibits retinoblastoma protein (pRb) phosphorylation, thereby limiting the transcription of genes directly promoting mitosis, and we showed that Pax6 inhibits pRb phosphorylation and represses several genes involved in DNA replication. Our results indicate that Pax6’s modulation of the cell cycles of cortical progenitors is regional and direct.
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Overall design |
Two condition experiment, Pax6sey/sey vs Pax6+/+ cortical progenitor cells from lateral cortex. 3 biological replicates. Each replicate contains RNA from cells pooled from 4 individual E12.5 embryos
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Contributor(s) |
Price DJ, Simpson TI |
Citation(s) |
23622063 |
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Submission date |
Jun 13, 2012 |
Last update date |
May 13, 2013 |
Contact name |
Ian Simpson |
URL |
http://neuroregulatorygenomics.org
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Organization name |
University of Edinburgh
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Department |
Institute for Adaptive and Neural Computation
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Lab |
School of Informatics
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Street address |
10 Crichton Street
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City |
Edinburgh |
ZIP/Postal code |
EH8 8AB |
Country |
United Kingdom |
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Platforms (1) |
GPL2872 |
Agilent-012694 Whole Mouse Genome G4122A (Feature Number version) |
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Samples (3) |
GSM947967 |
Mutant vs WT Cortical Progenitor Cells Replicate 1 |
GSM947968 |
Mutant vs WT Cortical Progenitor Cells Replicate 2 |
GSM947969 |
Mutant vs WT Cortical Progenitor Cells Replicate 3 |
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Relations |
BioProject |
PRJNA168450 |