NeuroSIGN

Understanding How NR2F1 Controls Retinal Regionalization During Development

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare neurodevelopmental disorder caused by mutations in the NR2F1 gene, a key regulator of brain and eye development. A major clinical feature of the syndrome is severe visual impairment; however, the developmental mechanisms underlying these visual deficits remain poorly understood.

The goal of our project is to elucidate how NR2F1 regulates the establishment of distinct retinal regions during embryonic development. To address this question, we use several mouse models carrying patient-derived NR2F1 mutations and characterize the molecular programs governing retinal cell development using single-cell RNA sequencing (scRNA-seq).

The MSI will provide us with the bioinformatics expertise required to analyze these large-scale transcriptomic datasets. These analyses will enable us to identify the retinal cell populations most affected by NR2F1 loss of function, gain mechanistic insight into the molecular pathways that regulate retinal development, and uncover the biological processes disrupted in BBSOAS.

Our preliminary findings suggest that NR2F1 regulates a molecular program involving retinoic acid signaling, a critical molecule required for the proper patterning of distinct retinal domains during development. Ongoing analyses will further define how disruption of this program affects the generation of specific retinal cell types and, ultimately, the development of high-acuity vision.

This project will advance our understanding of the developmental mechanisms underlying the visual deficits observed in patients with BBSOAS. By establishing a mechanistic link between early defects in retinal development and subsequent visual dysfunction, our work will identify novel biological targets and lay the foundation for the development of targeted therapeutic strategies.