title: Polycomb repressive complex PRC2 regulates Xenopus retina development downstream of Wnt/β-catenin signaling.
abstract: The histone methyltransferase complex PRC2 controls key steps in developmental transitions and cell fate choices; however, its roles in vertebrate eye development remain unknown. Here, we report that in Xenopus, PRC2 regulates the progression of retinal progenitors from proliferation to differentiation. We show that the PRC2 core components are enriched in retinal progenitors and downregulated in differentiated cells. Knockdown of the PRC2 core component Ezh2 leads to reduced retinal progenitor proliferation, in part due to upregulation of the Cdk inhibitor p15(Ink4b). In addition, although PRC2 knockdown does not alter eye patterning, retinal progenitor gene expression or expression of the neural competence factor Sox2, it does cause suppression of proneural bHLH gene expression, indicating that PRC2 is crucial for the initiation of neural differentiation in the retina. Consistent with this, knocking down or blocking PRC2 function constrains the generation of most retinal neural cell types and promotes a Müller glial cell fate decision. We also show that Wnt/β-catenin signaling acting through the receptor Frizzled 5, but independent of Sox2, regulates expression of key PRC2 subunits in the developing retina. This is consistent with a role for this pathway in coordinating proliferation and the transition to neurogenesis in the Xenopus retina. Our data establish PRC2 as a regulator of proliferation and differentiation during eye development.
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
authors.forename: Issam
authors.initials: I
authors.lastname: Aldiri
authors.forename: Kathryn B
authors.initials: KB
authors.lastname: Moore
authors.forename: David A
authors.initials: DA
authors.lastname: Hutcheson
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhang
authors.forename: Monica L
authors.initials: ML
authors.lastname: Vetter
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D000071221:Enhancer of Zeste Homolog 2 Protein; D051157:Frizzled Receptors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism; D008745:Methylation; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D060449:Wnt Signaling Pathway; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology*
chemical_list: C491487:EED protein, Xenopus; D051157:Frizzled Receptors; D006657:Histones; D012097:Repressor Proteins; D029867:Xenopus Proteins; C583224:EZH2 protein, Xenopus; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; C547734:Suz12 protein, Xenopus
keywords: Epigenetics; Ezh2; Histone methylation; Neurogenesis; Retina development; Wnt signaling