Innovative new research has identified hundreds of genes essential for the development of brain cells, including one linked to a previously unreported severe neurodevelopmental disorder.
The findings, detailed in a new study, resulted from work that focused on mapping the genes associated with neurodevelopmental disorders, such as autism and developmental delay. The research was led by Prof. Sagiv Shifman of The Institute of Life Sciences at The Hebrew University of Jerusalem, in collaboration with Prof. Binnaz Yalcin from INSERM, France.
In their study, the researchers focused on a primary question: which genes are required for embryonic stem cells to become brain cells, and what happens when this process fails?
To answer this, researchers conducted a genome-wide CRISPR “knockout” screen, switching off roughly 20,000 genes in embryonic stem cells and observing their ability to differentiate into neurons. By disrupting each gene separately, they could determine which ones were important for normal neural development.
“Using genome-wide CRISPR knockout screens to identify genes that are needed for early brain development. We use CRISPR to generate mutations across all genes in the genome, in a way that ensures each cell carries a different mutation,” Shifman told The Debrief in an email. “This creates millions of distinct mutations.
“We then grow these cells and differentiate them into progenitors and neurons,” Shifman added. “If a mutation disrupts the cell’s ability to develop or differentiate properly, we can detect it. In this way, we can identify mutations that were previously unrecognizable.”
The Study
The CRISPR screening identified 331 genes critical for neuron formation, many of which were previously unknown. In doing so, the technique was able to produce an “essentiality map” that offers researchers new perspectives on the genetics of neurodevelopmental disorders, including autism, developmental delay, and abnormality in brain size.
Additionally, the study uncovered the PEDS1 gene as the cause of a newly described neurodevelopmental disorder. PEDS1 is vital for making certain fats that protect and support brain cells, and without it, nerve cells don’t form properly, which can lead to a smaller brain.
The research team’s next step involved genetic testing, and by studying two families with rare PEDS1 mutations that caused severe developmental delays and small brains, they found that PEDS1 is vital for proper brain cell growth and movement, which helps to explain the underlying cause of the disorder.
“By tracking stem cell differentiation into neural cells and systematically disrupting nearly all genes in the genome, we created a map of the genes essential for brain development,” Shifman explained in a statement. “Identifying PEDS1 as a cause of developmental impairment opens the door to better diagnosis, genetic counseling, and potentially targeted therapies.”
Additionally, the study showed that different genes affect various conditions in differing ways. For instance, genes needed for many basic brain processes were linked to developmental delays. By contrast, genes involved explicitly in making new brain cells were more strongly associated with autism.
Early Brain Development
In addition to the identification of factors underlying various neurodevelopmental conditions, the new research advances our understanding of early brain development compared to past studies.
“Traditionally, previous studies focus on specific genes, typically one gene at a time,” Shifman said. “In contrast, our method is more systematic because we screen all genes across the genome.”
“Because this is an unbiased approach, we were able to identify many genes that had not been previously implicated,” Shifman added. “We then followed up on several of these genes in cell culture, examining how the mutations affected differentiation into neural cells. We also characterized eight additional genes in terms of their effects on brain structure.
“For one of them, we conducted a more in-depth analysis of its impact on cortical development and neuronal migration,” Shifman says.
Overall, the team’s research could offer important new data that may aid in predicting other genes linked to neurodevelopmental disorders in the future. Shifman notes that his team has already demonstrated this in the context of a single gene, though adding that “the same method can be applied to identify additional genes.”
The team’s study, “CRISPR knockout screens reveal genes and pathways essential for neuronal differentiation and implicate PEDS1 in neurodevelopment,” appeared in Nature Neuroscience on January 5, 2026.
Chrissy Newton is a PR professional and the founder of VOCAB Communications. She currently appears on The Discovery Channel and Max and hosts the Rebelliously Curious podcast, which can be found on YouTube and on all audio podcast streaming platforms. Follow her on X: @ChrissyNewton, Instagram: @BeingChrissyNewton, and chrissynewton.com. To contact Chrissy with a story, please email chrissy @ thedebrief.org.