Retinal development requires the timely and coordinated generation of neural and glial cell types from retinal progenitor cells (RPCs). This process is regulated by DNA methylation through the activity of various proteins, including the DNA-binding protein UHRF1. Now, Timothy Hallstrom and colleagues identify a new role for UHRF2, a paralog of UHRF1, in controlling the differentiation of mouse retinal progenitors. They find that Uhrf2 deletion causes excess proliferation and thus retinal hypercellularity during postnatal development, potentially resulting from changes in the expression and post-translational modification of cell cycle regulators. Moreover, loss of UHRF2 leads to a reduction in RPCs and delays the production of cone cells, whereas retinal ganglion cells are overproduced. The development of late cells, namely rods, bipolar cells, horizontal cells and Müller glia, is also delayed in Uhrf2-knockout mice. The authors further show that the levels of 5-hydroxymethylcytosine (5hmC), a DNA modification regulating cellular differentiation, are reduced during retinal development upon Uhrf2 deletion. Specifically, 5hmC in the gene body of genes within the active demethylation pathway, which produces 5hmC, are decreased. This coincides with their lower expression and could contribute to the overall loss of 5hmC in retinal progenitors. Collectively, these findings establish UHRF2 as a novel epigenetic regulator of gene expression and the cell cycle in retinal development.
Ensuring timely differentiation during retinal development
Ensuring timely differentiation during retinal development. Development 15 March 2022; 149 (6): e149_e0601. doi:
Download citation file:
Advertisement
Cited by
Development presents... live stream of our upcoming Journal Meeting

Watch a session from Development’s next Journal Meeting, Unconventional and Emerging Experimental Organisms in Cell and Developmental Biology live on the Node on Monday 18 September at 16:00 BST (15:00 UTC).
Navigating a research career with a disability

Our two recent Perspectives articles explore the lived experiences of disabled scientists in our community. Kelsey L. Anbuhl and colleagues describe the lived experiences of five biologists who share the challenges and successes of undertaking a scientific career with a disability. Whereas Jack Darius Morgan reviews the literature exploring disabled scientists’ experiences in academia.
Focus on regeneration

Tissue regeneration is a fascinating phenomenon, but the cellular and molecular mechanisms underlying regeneration remain incompletely understood. Here, Development has collated a series of articles showcasing some of the most recent advances in regenerative biology.
Keeping up with the Node: Lab meetings

Keep up with the Node 'Lab meeting' posts as the platform regularly highlights development and stem cell biology labs from across the globe and showcases research and researchers from the community. August featured the Nichols lab at the University of Edinburgh, read their 'Lab meeting' article here.
Read & Publish Open Access publishing: what authors say

We have had great feedback from authors who have benefitted from our Read & Publish agreement with their institution and have been able to publish Open Access with us without paying an APC. Read what they had to say.