title: Polycomb Ezh2 controls the fate of GABAergic neurons in the embryonic cerebellum.
abstract: Although the genetic interactions between signaling pathways and transcription factors have been largely decoded, much remains to be learned about the epigenetic regulation of cerebellar development. Here, we report that cerebellar deletion of Ezh2, the methyltransferase subunit of the PRC2 complex, results in reduced H3K27me3 and profound transcriptional dysregulation, including that of a set of transcription factors directly involved in cerebellar neuronal cell-type specification and differentiation. Such transcriptional changes lead to increased GABAergic interneurons and decreased Purkinje cells. Transcriptional changes also inhibit the proliferation of granule precursor cells derived from the rhombic lip. The loss of both cell types ultimately results in cerebellar hypoplasia. These findings indicate Ezh2/PRC2 plays crucial roles in regulating neurogenesis from both cerebellar germinal zones.
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Feng
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA.
authors.forename: Aster H
authors.initials: AH
authors.lastname: Juan
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA.
authors.forename: Hongjun A
authors.initials: HA
authors.lastname: Wang
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA.
authors.forename: Kyung Dae
authors.initials: KD
authors.lastname: Ko
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA.
authors.forename: Hossein
authors.initials: H
authors.lastname: Zare
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health, 50 South Drive, Bethesda, MD 20892, USA sartorev@mail.nih.gov.
authors.forename: Vittorio
authors.identifier: 0000-0002-9284-3675
authors.initials: V
authors.lastname: Sartorelli
mesh_terms: D000818:Animals; D002452:Cell Count; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D002531:Cerebellum / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D059330:GABAergic Neurons / Q000166:cytology* / Q000378:metabolism*; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci; D016678:Genome; D006657:Histones / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D018345:Mice, Knockout; D051763:PAX7 Transcription Factor / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D006657:Histones; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D025521:Tumor Suppressor Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; D008239:Lysine
keywords: Cerebellum; Ezh2; Neurogenesis; PRC2; Polycomb; Purkinje cells