The polycomb repressive complex PRC2 regulates proliferation and neurogenesis in the Xenopus retina, and is governed by Wnt/beta-catenin signaling

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 with differentiation. Knockdown of the PRC2 core component Ezh2 leads to reduced retinal progenitor proliferation in part due to upregulation of the cdk inhibitor p15Ink4b. In addition, while 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 critical 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 Mueller 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 establishes PRC2 as a regulator of proliferation and differentiation during eye development.

Dataset features

Information

Specifications

Application:	Gene expression microarray analysis
Number of samples:	8
Release date:	May 30 2013
Last update date:	Dec 29 2014
Access:	Public
Diseases:	Retinal Neoplasms
Dataset link	The polycomb repressive complex PRC2 regulates proliferation and neurogenesis in the Xenopus retina, and is governed by Wnt/beta-catenin signaling

Experimental Protocol

Xenopus embryos were injected at the 8-cell stage with 5ng Ezh2 ATG MO or 5ng control MO (scrambled sequence of Ezh2 ATG MO) together with 400 pg mRNA for GFP as a lineage tracer. At stage 27, GFP-positive eyes were isolated by microdissection. Pools of 20-25 eyes were used to prepare total RNA for each sample on the microarray. 4 control and 4 Ezh2 ATG MO samples were hybridized to Agilent 1-color microarrays.

Repositories

GEO

GSE47456

ArrayExpress

E-GEOD-47456

BioProject

PRJNA205635

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Contact

Brett Milash