Jerusalem Post

ByPESACH BENSON/TPS, OMER NOVOSELSKY/TPS

An international team of scientists has identified hundreds of genes that are essential for early brain development, uncovering new insights into the biological roots of neurodevelopmental disorders, including autism, and describing a previously unknown genetic condition that disrupts brain growth, the Hebrew University of Jerusalem announced.
The study, published in the peer-reviewed journal Nature Neuroscience, used large-scale CRISPR gene-editing technology to systematically determine which genes are required as embryonic stem cells developed into brain cells.

Led by Prof. Sagiv Shifman of Hebrew University’s Institute of Life Sciences in collaboration with Prof. Binnaz Yalcin of INSERM in France, the team of Israeli, French, and Japanese scientists set out to answer a fundamental question in neuroscience: which genes are necessary for building a healthy brain, and what happens when that process fails?

Using a genome-wide CRISPR knockout screen, the researchers individually disabled nearly 20,000 genes in embryonic stem cells as they transitioned into neural cells. This allowed the team to observe, step by step, which genes were indispensable for normal neural differentiation. In simple terms, neural differentiation is how a generic early cell learns to become a brain or nerve cell. Through this approach, the scientists identified 331 genes that are essential for generating neurons, many of which had not previously been linked to brain development.

While the findings span a wide range of neurodevelopmental conditions, the implications for autism stood out in both the data and in The Press Service of Israel’s interview with Shifman. The study’s results suggest that not all neurodevelopmental disorders arise from the same types of genetic disruptions and that timing during brain development plays a critical role.

Autism risk genes emerge
“The study delivers a genome-wide, stage-resolved essentiality map of neural differentiation,” Shifman told TPS-IL. “By knocking out about 20,000 genes during the transition from embryonic stem cells to neural lineages, we identified 331 genes required for neuronal generation and showed how this map can both interpret human genetic risk and help discover new neurodevelopmental disease genes.”