Study identifies critical role of epigenetic regulation in rod photoreceptor specification
Ismael Hernández-Núñez, PhD, researcher in the Clark lab at WashU Medicine John F. Hardesty, MD Department of Ophthalmology & Visual Sciences, and his laboratory recently published “Active DNA demethylation upstream of rod-photoreceptor fate determination is required for retinal development”. The study uncovers how changes to DNA modifications help guide the development of the retina.
The Clark lab investigates how the diverse cell types of the retina arise from retinal progenitor cells. In this study, the team showed that the removal of DNA methylation marks—through a process called DNA demethylation regulated by TET enzymes—is required for rod photoreceptor specification. Loss of these enzymes prevented the expression of master transcription factors NRL and NR2E3, identifying a novel mechanism that determines how retinal cells develop into rods.
“Our study highlights the relevance of 5hmC during retinal development and the requirement of TET enzymes and active DNA demethylation for rod-photoreceptor fate specification and visual function,” said Hernandez Nunez.
“This work highlights the complexity of how gene expression is regulated to generate nervous system diversity,” said Brian Clark, PhD. “Our studies emphasize the biological functions of DNA modifications such as 5-methyl cytosine and 5-hydroxymethyl cytosine in retinal development, and provide insights into how environmental insults or aging can lead to reduced retinal function and disease.”
About WashU Medicine
WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,900 faculty. Its National Institutes of Health (NIH) research funding portfolio is the second largest among U.S. medical schools and has grown 56% in the last seven years. Together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,900 faculty physicians practicing at 130 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.