PROJECT: JTC2021 - Neurodevelopmental Disorders: Brain4Sight

Deconstructing gene regulatory networks for improving sight and brain disabilities


Neurodevelopmental disorders (NDD) are complex conditions frequently arising from failed developmental processes. NDD display heterogeneous clinical features often including vision defects. Conversely, NDD affecting the visual system (VS) display comorbidities affecting the brain, also with variable degrees and frequencies. This makes NeuroDevelopmental Visual Disorders (NDVD) an excellent paradigm to understand NDD phenotypic variability. This variability is often associated with overlapping phenotypes among different NDVD, which further complicates a genetic diagnosis. By delving into the processes of brain assembly, Brains4Sight seeks to understand the region-specific susceptibility and phenotypic variability that emerges as the consequence of monogenic pathogenic variants in SOX2 and NR2F1. These genes encode transcription factors essential for VS development and their mutated versions are respectively responsible for syndromic anophthalmia/microphthalmia and the BBSOA syndrome. Brains4Sight will employ state-of-the-art genomic technologies, mouse models and human cortical and eye organoids to address the mechanisms underlying the symptoms associated with specific variants of these genes. The knowledge gained will be applied to reprogramme endogenous glia cells into neurons with the long-term aim of reconstructing a healthy VS. Thus, Brains4Sight will provide critical knowledge towards NDVD therapeutics, further impacting genetic consulting and thereby health care


Gene targeting in the brain, Stem cells and neural differentiation/cell therapy, Molecular modelling techniques, Imaging techniques, omics approaches, Sox2, organoids, Animal studies, Visual Disorders, Anophthalmia, Microphthalmia, Bosch-Boonstra-Schaaf optic atrophy syndrome, NR2F1, in vivo reprogramming

Call topic

Neurodevelopmental Disorders

Proposed runtime

n/a - n/a

Project team

Paola Bovolenta (Coordinator)
Spain (AEI)
Michele Studer
France (ANR)
Silvia Russo
Italy (MOH)
Benedikt Berninger
Germany (BMBF)

Lay summary