Gene-by-gene CRISPR screen maps brain development and finds a new childhood disorder

A study published in Nature Neuroscience on 5 January 2026 offers one of the most complete maps yet of the genes a developing brain cannot do without. The work was led by Professor Sagiv Shifman of the Hebrew University of Jerusalem's Alexander Silberman Institute of Life Sciences, with Professor Binnaz Yalcin of France's INSERM, and included researchers in Israel, France, the Palestinian territories and Japan.

The team used genome-wide CRISPR knockout screens on embryonic stem cells as they matured into nerve cells, switching off roughly 20,000 genes one at a time to see which ones the transition depends on. They found 331 genes essential for producing neurons, many of which had never been tied to brain development. Among them was PEDS1, a gene needed to make plasmalogens, fatty molecules that are abundant in myelin, the insulating sheath around nerve fibres. Losing PEDS1 reduced brain size in the screen.

Genetic testing then turned up a rare PEDS1 mutation in two children from two unrelated families, both with developmental delay and unusually small brains. Further experiments confirmed that the gene is needed for nerve cells to form and migrate normally, establishing a previously undescribed neurodevelopmental disorder. The data also revealed broader patterns: disorders caused by genes that regulate other genes tend to be dominant, while those caused by metabolic genes such as PEDS1 tend to be recessive, and genes needed specifically during neuron formation were more strongly linked to autism.

The researchers have released their results as a free online database so that other scientists and clinicians can look up genes of interest. The work was funded in part by the Israel Science Foundation.