Study finds impact of specific gene on neurodevelopment, causing ASD and macrocephaly

During the developmental phase of brains, several moving parts occur—and if mutations occur during the early neurodevelopment, it can result in disorders such as autism and macrocephaly.

Autism Awareness

Image Credit: SewCream/

However, there is a lack of knowledge among researchers about how the development gets distorted, especially in humans.

This is the reason for Wei Zhang’s curiosity. He wanted to know how certain genes can influence early brain development. Zhang is a research associate and postdoctoral scholar at USC’s Center for Craniofacial Molecular Biology.

Zhang and his team had already chosen a specific gene named RAB39b from an earlier study. They searched the scientific literature to gain more insights into this gene and its properties.

According to Zhang, it was reported that RAB39b is as an autism spectrum disorder (ASD) risk gene, associated with the X chromosome. A mutation in this gene could result in intellectual disability, macrocephaly, epilepsy, ASD, and early-onset Parkinson’s disease.

However, the functional study of RAB39b is very limited, and the mechanism of RAB39b mutation leading to macrocephaly and ASD is not clear.”

Wei Zhang, Research Associate and Postdoctoral Scholar, Center for Craniofacial Molecular Biology, University of Southern California

The researchers were fascinated and decided to analyze further.

ASD/Macrocephaly falls into a subset of autism. The brain surface area of a baby who will develop autism/macrocephaly tends to hyper-expand in the weeks immediately before and after birth.

Then, it continues to enlarge further than normal following birth, leading to the occurrence of autistic social deficits. This is precisely why brain development studies are crucial for investigating the mechanism of ASD, stated Zhang.

A system had already been developed in Zhang’s lab to investigate brain development with the help of a mouse model and human brain organoids, or miniature brains artificially grown in the laboratory.

A decade ago, these organoids originated as pea-sized objects that were grown from human stem cells self-organizing into brain-like structures consisting of electrically active neurons.

They have been useful in findings on Zika-associated microcephaly, schizophrenia, and even to test new drugs.

Zhang and his team use the two models to delete the RAB39B gene in the human brain organoid and the mice. The mice exhibited signs of autism-like behaviors and macrocephaly. The human brain organoids were found to be enlarged and affected by the removal of the gene.

According to Zhang, the study demonstrates how a mutation in this gene interferes with growth and differentiation of what is called the neural progenitor cells, which eventually develop into different types of brain cells.

That can eventually cause autism-like behaviors and macrocephaly. The study was directed and conducted in the laboratory of Jianfu Chen, an assistant professor of USC, and was reported last month in the Genes and Development journal. Yang Chai Ph.D. ’91, DDS ’96, who is the Associate Dean of Research, also contributed to the study.

The Centers for Disease Control’s Autism and Developmental Disabilities Monitoring Network reports that nearly 1 in 59 children have been identified with autism spectrum disorder.

According to Zhang, this study can offer a fresh understanding of neurodevelopmental dysregulation and common pathways associated with autism disorders and macrocephaly over a wide range of species.

Since it is now evident that this gene plays a crucial role in regulating the growth of new brain cells, Zhang and his team intend to study RAB39b’s role in regulating neuron activity-dependent signaling networks, to further investigate the mechanism of autism spectrum disorder.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of AZoLifeSciences.
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