Loss of Ezh2 promotes a midbrain-to-forebrain identity switch by direct gene derepression and Wnt-dependent regulation
| Autor: | Martina Zemke, Kalina Draganova, Annika Klug, Anne Schöler, Luis Zurkirchen, Max Hans-Peter Gay, Phil Cheng, Haruhiko Koseki, Tomas Valenta, Dirk Schübeler, Konrad Basler, Lukas Sommer |
|---|---|
| Přispěvatelé: | University of Zurich, Sommer, Lukas |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
10017 Institute of Anatomy
Physiology Plant Science Epigenesis Genetic 1309 Developmental Biology 1307 Cell Biology Mice 1315 Structural Biology Mesencephalon Structural Biology Gene expression 1110 Plant Science Wnt Signaling Pathway Derepression Agricultural and Biological Sciences(all) EZH2 Polycomb Repressive Complex 2 Wnt signaling pathway Gene Expression Regulation Developmental 10124 Institute of Molecular Life Sciences Cell biology FOXG1 Brain area identify 1305 Biotechnology Epigenetics General Agricultural and Biological Sciences Research Article Biotechnology 610 Medicine & health macromolecular substances 1100 General Agricultural and Biological Sciences Biology General Biochemistry Genetics and Molecular Biology Prosencephalon 1300 General Biochemistry Genetics and Molecular Biology Animals Enhancer of Zeste Homolog 2 Protein Ezh2 Ecology Evolution Behavior and Systematics Neural stem cells Biochemistry Genetics and Molecular Biology(all) Cell Biology 1314 Physiology Midbrain development Molecular biology 1105 Ecology Evolution Behavior and Systematics Forebrain 570 Life sciences biology Ectopic expression PAX6 Wnt/β-catenin signaling Developmental Biology |
| Zdroj: | BMC Biology |
| DOI: | 10.5167/uzh-115847 |
| Popis: | 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, which catalyzes trimethylation of histone H3K27 (H3K27me3) and thereby represses gene expression. Results Herein, we show that Ezh2 plays a crucial role in the 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 maintenance of regional identity by H3K27me3-mediated gene repression and control of canonical Wnt signaling. Electronic supplementary material The online version of this article (doi:10.1186/s12915-015-0210-9) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|