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Development. 2016 Jun 1;143(11):1971-80. doi: 10.1242/dev.132902. Epub 2016 Apr 11.

Polycomb Ezh2 controls the fate of GABAergic neurons in the embryonic cerebellum.

Author information

1
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.
2
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.

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.

KEYWORDS:

Cerebellum; Ezh2; Neurogenesis; PRC2; Polycomb; Purkinje cells

PMID:
27068104
PMCID:
PMC4920161
DOI:
10.1242/dev.132902
[Indexed for MEDLINE]
Free PMC Article

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