Summary: A brain organoid study reveals how a genetic mutation associated with Pitt-Hopkins syndrome, a profound form of autism, disrupts neural development. Using gene-editing technology, researchers recovered the function of the TCF4 gene and effectively restored neural structure and function.
Source: UCSD
In a study published in Nature Communications, scientists at University of California San Diego School of Medicine used human brain organoids to reveal how a genetic mutation associated with a profound form of autism disrupts neural development.
Using gene therapy tools to recover the gene’s function effectively rescued neural structure and function.
Several neurological and neuropsychiatric diseases, including autism spectrum disorders (ASD) and schizophrenia have been linked to mutations in Transcription Factor 4 (TCF4), an essential gene in brain development.
Transcription factors regulate when other genes are turned on or off, so their presence, or lack thereof, can have a domino effect in the developing embryo. Still, little is known about what happens to the human brain when TCF4 is mutated.
To explore this question, researchers focused on Pitt-Hopkins Syndrome, an ASD specifically caused by mutations in TCF4. Children with the genetic condition have profound cognitive and motor disabilities and are typically non-verbal.
Existing mouse models of Pitt-Hopkins Syndrome fail to accurately mimic patients’ neural characteristics, so the UC San Diego team instead created a human research model of the disorder. Using stem cell technology, they converted patients’ skin cells into stem cells, which were then developed into three-dimensional brain organoids, or “mini-brains.”
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