A new genetic study has identified 331 genes essential for transforming stem cells into brain cells, including a novel gene linked to neurodevelopmental disorders. Led by scientists at the Hebrew University of Jerusalem, the research highlights how early genetic disruptions can lead to conditions like autism and developmental delay. The findings, published in Nature Neuroscience, also reveal patterns in how these disorders are inherited.
Scientists have mapped the genetic blueprint of early brain development through a comprehensive screen of nearly 20,000 genes using CRISPR technology. The study, published on January 5, 2026, in Nature Neuroscience, was spearheaded by Prof. Sagiv Shifman at the Hebrew University of Jerusalem, in partnership with Prof. Binnaz Yalcin at INSERM in France. By disabling genes one by one in embryonic stem cells as they differentiated into neural cells, the team pinpointed 331 genes crucial for neuron production—many previously unlinked to this process.
A standout discovery is the gene PEDS1, which produces plasmalogens, lipids vital for myelin that insulates nerve fibers. Loss of PEDS1 impairs nerve cell formation and brain growth, tying it to a newly identified neurodevelopmental disorder. Genetic analysis of two unrelated families revealed rare PEDS1 mutations in children exhibiting severe developmental delays and reduced brain size. Experiments disabling the gene in models confirmed these effects, showing disrupted cell migration and formation.
Prof. Shifman explained: "By tracking the differentiation of embryonic stem cells into neural cells and systematically disrupting nearly all genes in the genome, we created a map of the genes essential for brain development. This map can help us better understand how the brain develops and identify genes linked to neurodevelopmental disorders that have yet to be discovered."
The research also distinguishes inheritance patterns: transcription and chromatin genes often cause dominant disorders from a single mutation, while metabolic genes like PEDS1 lead to recessive conditions requiring changes in both copies. An "essentiality map" further separates genes tied to autism—key during neuron formation—from those linked to developmental delay, active across broader stages.
Funded by the Israel Science Foundation and others, the team released an open database at https://aa-shifman.shinyapps.io/Neuro_Diff_Screen/ to aid global research. These insights could enhance diagnosis, counseling, and targeted therapies for neurodevelopmental issues.
