Study: Defective EMC1 protein may contribute to a severe ocular disorder, familial exudative vitreoretinopathy


Researchers note their work reports a novel candidate gene for FEVR, which expands the spectrum of EMC1 variants and EMC1-related phenotypes, providing evidence for the prenatal diagnosis of candidate disease-causing EMC1 variants in FEVR.

©Kritdanai /

(Image Credit: ©Kritdanai -

A team of researchers from University of Electronic Science and Technology of China have uncovered a link between the EMC1 protein and retinal vascular development.

The study1 was published recently in Genes & Diseases.

According to researchers, mutations in the EMC1 gene appear to be associated with FEVR, a severe ocular condition. The discovery offers potential new therapeutic avenues for treating this disorder and other related vascular defects.

Chongqing Medical University noted in a news release that researchers have found the depletion of Emc1 in endothelial cells in mice causes significant defects in retinal vessel development, including reduced vascular growth and retinal bleeding. This impairment is intricately linked with the Wnt signaling pathway, a critical regulator for blood vessel development, whose gene activity is altered when EMC1 is compromised.

The researchers, according to the university news release, noted the study prompted them to look at the EMC1 gene in patients with FEVR, leading to the identification of a genetic variant in 2 related patients, suggesting a potential genetic connection.

“We generated an endothelial cell-specific knockout model for Emc1 and assessed its role in retinal angiogenesis,” the researchers wrote in the study.

The researchers noted Emc1 deletion in endothelial cells led to aberrant retinal vascularization, manifesting reduced vascular progression and vascular density, diminished tip cell sprouts, and vascular leakage. Using an unbiased RNA transcriptomics analysis and in-vitro experiments, we revealed a pivotal role of EMC1 in Wnt signaling.

“By screening FEVR samples with high-throughput whole-exome sequencing, we identified a heterozygous missense variant in EMC1 gene that is associated with FEVR,’ the researchers wrote. “The mutant EMC1 protein led to compromised β-catenin signaling activity via diminished expression of FZD4 receptor. Our study uncovers the essential role of EMC1 in retinal vascularization and sheds light on the importance of EMC in the regulation of β-catenin signaling during retinal angiogenesis.”

Moreover, the researchers noted treating EMC1-depleted cells with LiCl, an activator of the Wnt signaling pathway, mitigated some of the adverse effects, hinting at potential therapeutic avenues for conditions associated with EMC1 dysfunction. The EMC1 protein has emerged as a pivotal factor in retinal blood vessel development, operating primarily via the Wnt signaling pathway.

According to the university news release, variants in the EMC1 gene found in FEVR patients can divert this process, shedding light on potential causes and treatment avenues for the condition.

“This discovery enhances our understanding of FEVR’s origins and broadens the horizon for targeted therapeutic interventions,” the researchers wrote.

By focusing on the Wnt signaling pathway, the researchers hope to develop treatments that could alleviate or even reverse the vascular defects associated with compromised EMC1 function.

“We demonstrate the regulatory role of EMC1 in retinal vascularization via FZD4/β-catenin axis,” the researchers concluded. “Additionally, we identify one heterozygous variant in EMC1 gene that is causative for FEVR and illustrate the mechanism of the variant with down-regulated β-catenin signaling activity. Thus, our study reports a novel candidate gene for FEVR, which expands the spectrum of EMC1 variants and EMC1-related phenotypes, providing evidence for the prenatal diagnosis of candidate disease-causing EMC1variants in FEVR.”

  1. Shujin Li, Mu Yang, Rulian Zhao, Li Peng, Wenjing Liu, Xiaoyan Jiang, Yunqi He, Erkuan Dai, Lin Zhang, Yeming Yang, Yi Shi, Peiquan Zhao, Zhenglin Yang, Xianjun Zhu, Defective EMC1 drives abnormal retinal angiogenesis via Wnt/β-catenin signaling and may be associated with the pathogenesis of familial exudative vitreoretinopathy, Genes & Diseases, Volume 10, Issue 6, 2023, Pages 2572-2585, ISSN 2352-3042,
© 2024 MJH Life Sciences

All rights reserved.