Rare genetic disorder opens window into the social brain

Scientists hope that a neurodevelopmental model of Williams syndrome will lead to broader insight into the human social brain

Researchers from the University of California San Diego have developed a neurodevelopmental model of a rare genetic disorder that could help shed light on the workings of the human social brain.

Williams syndrome (WS) is caused by the deletion of one copy of 25 genes located next to each other on chromosome 7 and affects 1 in 10,000 people worldwide. The disorder is associated with a range of medical problems such as cardiovascular disease, and individuals with WS typically have distinctive facial features consisting of a wide mouth, full lips and small chin.

WS is also linked to with neurological problems such as spatial deficits and developmental delays, but unlike autism, children with WS can have a highly social and trusting nature, as well as strong language and facial processing abilities and an affinity for music.

"I was fascinated on how a genetic defect, a tiny deletion in one of our chromosomes, could make us friendlier, more empathetic and more able to embrace our differences," says Alysson Muotri, an associate professor from UC San Diego and co-senior author of the study.

In previous research Muotri had used reprogrammed induced pluripotent stem cells (iPSCs) from teeth to create cellular models of autism, a method that was applied to WS for the current study.

Using dental pulp cells obtained from the teeth of children with WS, the research team reprogrammed the stem cells in order to create neural progenitor cells. These cell types possess the ability to create neural networks that mirror the cortex of the human brain as it develops, all inside of a laboratory dish.

The results revealed that the WS neural progenitor cells were unable to thrive due to unusually high levels of cell death, leading to lower replication rates and a reduced surface area of the cortex. The team confirmed the reduced cortex surface area in the brains of human subjects with WS using magnetic resonance imaging.

In addition, when compared to neurons from individuals without WS, the cultured WS neurons show a distinct morphology, with many dendritic branches that give them a treelike appearance, and in turn more synapses and interconnectivity with other neurons. These laboratory findings were confirmed in WS postmortem brain tissue.

"At the functional level, they make more synapses or connections to other neurons than what you would expect," says Muotri. "That might underlie the WS super-social aspect and their gregarious human brain, giving insights into autism and other disorders that affect the social brain."

The findings from this WS neurodevelopmental model could eventually help uncover the specific neurobiology of the human brain that leads to the disparate social abilities in those with autism and WS. Understanding these biomarkers and cortical differences is important for the development of new therapeutic treatments and could also lead to a better understanding of the human social brain in general.

The research was published in the journal Nature.

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