 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Nov 09, 2015 |
| Title |
Loss of Ezh2 promotes a midbrain-to-forebrain identity switch by direct gene derepression and Wnt-dependent regulation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Background:
Precise spatiotemporal control of gene expression is essential for the establishment of correct cell numbers and identities during brain development. This process involves epigenetic control mechanisms, such as those mediated by the polycomb group protein Ezh2 that catalyzes trimethylation of histone H3K27 (H3K27me3) and thereby represses gene expression.
Results:
Here we show that Ezh2 plays a crucial role in development and maintenance of the midbrain. Conditional deletion of Ezh2 in the developing midbrain resulted in decreased neural progenitor proliferation, which is associated with derepression of cell cycle inhibitors and negative regulation of Wnt/β-catenin signaling. Of note, Ezh2 ablation also promoted ectopic expression of a forebrain transcriptional program involving derepression of the forebrain determinants Foxg1 and Pax6. This was accompanied by reduced expression of midbrain markers, including Pax3 and Pax7, as a consequence of decreased Wnt/β-catenin signaling.
Conclusion:
Ezh2 is required for appropriate brain growth and for maintenance of regional identity by H3K27me3-mediated gene repression and control of canonical Wnt signaling.
|
| |
|
| Overall design |
After tissue isolation from dorsal midbrains of embryonic day (E) 10.5 embryos, total RNA was isolated with the RNAeasy kit (Qiagen) and RNase-Free DNase Set (79254, Qiagen) following the manufacturer’s instructions. Isolated total RNA of E10.5 control (n=3, from 2 different litters) and Ezh2 cko (n=3, from 2 different litters) dorsal midbrains was used for microarray analysis performed at the Functional Genomics Center Zurich (FGCZ), Switzerland, using the Affymetrix A430 platform.
|
| |
|
| Contributor(s) |
Zemke M, Draganova K, Klug A, Schöler A, Zurkirchen L, Gay MH, Cheng P, Koseki H, Valenta T, Schübeler D, Basler K, Sommer L |
| Citation(s) |
26621269 |
| Submission date |
Oct 30, 2015 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Martina Zemke |
| Organization name |
University Zurich
|
| Department |
Institute of Anatomy
|
| Lab |
Lukas Sommer
|
| Street address |
Winterthurerstrassse 190
|
| City |
Zurich |
| ZIP/Postal code |
8057 |
| Country |
Switzerland |
| |
|
| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA300674 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE74538_RAW.tar |
22.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Raw data provided as supplementary file |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...