CRISPR Screen Unlocks Secrets of Human Brain Development, Says University of Jerusalem Study

CRISPR Screen Reveals Human Brain Development

How can a single stem cell understand that it must become a brain cell? Which genes are guiding this life-defining process? The University of Jerusalem has brought science closer to answering these questions through groundbreaking research. This research reveals a hidden genetic blueprint for human brain development through the CRISPR Screen.

The research was published in Nature Neuroscience. It reveals that a large number of genes act like switches during the early stages of brain development. PEDS1 is one among them. PEDS1 is linked to a previously unknown neurodevelopmental disorder in children.

Huge CRISPR Screen Maps Early Brain Formation

CRISPR is one of the most powerful gene editing tools being used in modern discoveries and treatments. Researchers changed CRISPR to crack one of the toughest mysteries of biology. 

This research was led by Prof. Sagiv Shifman from the Institute of Life Sciences at the University of Jerusalem, and in collaboration with Prof. Binnaz Yalcin of INSERM, France. Nearly 20,000 genes were switched off one by one using this CRISPR gene-editing technology.

The research began with embryonic stem cells in the laboratory. They observed what happened when these stem cells changed into neurons. The development process failed if a gene was essential. The development process continued if the genes are non-essential.

This large-scale approach allowed the researchers to gain more insight into the essential genes involved in brain development.

331 Critical Genes Identified in Human Brain Development

The research team identified 331 genes that are essential for making neurons. Many of these genes had never before been linked to early human brain development. Some genes control how cells divide. Some guide how neurons migrate. And some help the young brain cells connect into networks. These interpretations help explain the genetic changes that can lead to conditions such as developmental delay, autism, or reduced brain size. 

PEDS1: A Hidden Gene Behind a New Brain Disorder

PEDS1 is involved in producing Plasmalogens. Plasmalogens are special fats found in the protective coating around nerve fibres called myelin. Until now, the role of PEDS1 in early brain development remains incompletely understood. 

This CRISPR Screen showed that neurons struggle to form and that brain growth is reduced in the absence of the PEDS1 gene. This lab discovery soon found real-world confirmation. Gene testing from two different families showed that children with severe developmental delay and smaller brains have rare mutations in the PEDS1 gene.

Further experiments confirmed that when PEDS1 was disabled, the nerve cells failed to develop and migrate normally. The gene was essential.

What does this mean for Families and Doctors?

Identifying PEDS1 as a disease-causing gene opens new doors, according to Prof. Shifman. He said they created a map of genes essential for brain development by disrupting all the genes in the genome and tracking brain cell development. This can improve disease diagnosis, support genetic counselling for families, and guide future treatment methods.  

CRISPR Screen Reveals Patterns of Inheritance

This research also revealed an important pattern in how brain disorders are inherited. Genes that control other genes are often linked to dominant disorders. In contrast, metabolic genes such as PEDS1 can cause recessive disorders, meaning that both gene copies must be altered. Understanding these gene patterns can help doctors prioritize which genes to test when diagnosing children

New Insights Into Autism and Developmental Delay

The researchers generated an essentiality map showing when the genes are required during brain development using the data collected. 

They found that: 

• Essential genes across multiple stages were more strongly associated with developmental delay.
• Genes critical during neuronal development were more closely associated with autism

This helps explain why these conditions are overlapping. This supports the idea that very early genetic alterations are responsible for the later brain function.

Open Data From the University of Jerusalem for Global Research

The research team launched an open online database to support the wider scientific community. This allowed the researchers to explore interpretations and accelerate new discoveries worldwide. This research was supported by the Israel Science Foundation, the  ISF-Broad Institute Program, and the MAVRI Biomedical Research Program.

A New Foundation for Brain Science

This research at the University of Jerusalem reveals one of the most detailed genetic maps for early brain development. A new standard for understanding the genetic roots of brain disorders has been created by combining a powerful CRISPR Screen, real patient data, and science.

Tiny and early changes in the genes can shape the entire human brain. Now, science finally knows where to look!