Table 1 Developmental effects of PRC2

Proper timing of neurogenesis

EZH2-KO in mice leads to premature exhaustion of the pool of neural progenitor cells, decreased neuronal density at the cortical plate, and precocious astrocyte generation

Pereira et al. [134]

EED-KO mice experience impaired neurogenesis, growth retardation, and death. EED ablation leads to abnormal neuronal differentiation during the hippocampal dentate gyrus formation

Liu et al. [152]

miR-203 is repressed by EZH2 in neural progenitor cells and negatively regulates proliferation. EZH2-KO results in the reduction of neural progenitor proliferation

Liu et al. [166]

Appropriate neuronal orientation and cortical radial migration

EZH2 inhibition results in abnormal neuronal orientation reduced neuronal numbers at the cortical plate and ectopic expression of Reelin

Zhao et al. [135]

EZH2-mediated repression of Netrin1 is necessary for the appropriate migration of pontine neurons in the cortico-ponto-cerebellar pathway in mice. EZH2-KO results in ectopic Netrin1 induction and aberrant neuronal migration

Di Meglio et al. [156]

Maintenance of neuronal identity

Deletion of EED disrupts the acquisition and maintenance of neuronal identity and functionality in differentiated dopaminergic and serotonergic neurons

Toskas et al. [153]

Conditional knock-out of EZH2 results in reduced proliferation of granule precursor cells, decrease in the Purkinje cell population and increase in GABAergic interneurons in the mouse cerebellum

Feng et al. [155]

Conditional KO of EZH2 results in loss of H3K27me3 marks in differentiating neurons and causes changes to molecular networks that govern glutamatergic neuron differentiation, leading to a disruption in the balance of inhibitory/excitatory neurons during the development

Buontempo et al. [132]

Combined EZH1 and EZH2 KO leads to a loss of H3K27me3 marks in MSNs in the striatum, down-regulation of lineage-specific and function-specific MSN genes, and upregulation of the death-promoting genes

Von Schimmelmann et al. [154]

Glial cell development and fate determination

Pharmacological inhibition of EZH2 leads to increased expression of Olig1 and Olig2. Increased depositions of H3K27me3 marks are detected in the genomic loci of Olig1 and Olig2 in HMGN-KO ESCs

Deng et al. [124]

KO of EZH2 or EED do not affect the generation of OPC but inhibit their differentiation into mature, myelinating oligodendrocytes. PRC2 is necessary for the repression of the Notch pathway

Wang et al. [160]

EZH2 regulates NSC differentiation into glial cells in mice, with high expression levels of EZH2 associated with increased oligodendrocyte production and decreased production of astrocytes while low levels of EZH2 correlate with a reduction in oligodendrocyte generation and increased numbers of astrocytes

Sher et al. [159]

Increased levels of EZH2 and EED mRNAs are detected during the early stage of OPC lineage commitment and development in mouse and human ESCs and human iPSCs

Douvaras et al. [162]