Autism Genes Activate During Fetal Brain Development

Autism Genes Activate During Fetal Brain Development
Scientists have found that mutations that cause autism in children are connected to a pathway that regulates brain development. The research is published in the journal Neuron.
The researchers studied a set of well-known autism mutations called copy number variants or CNVs. They investigated when and where the genes were expressed during brain development. They immediately observed that different CNVs seemed to be turned on in different developmental periods.
Specifically, the scientists noted that one CNV located in a region of the genome known as 16p11.2, contained genes active during the late mid-fetal period. Ultimately, they identified a network of genes that showed a similar pattern of activation including KCTD13 within 16p11.2 and CUL3, a gene from a different chromosome that is also mutated in children with autism.
The researchers realized that the proteins encoded by these genes form a complex that regulates the levels of a third protein, RhoA. Rho proteins play critical roles in neuronal migration and brain morphogenesis at early stages of brain development.
Further experiments confirmed that CUL3 mutations disrupt interaction with KCTD13, suggesting that 16p11.2 CNV and CUL3 may act via the same RhoA pathway. RhoA levels influence head and body size in zebrafish, a model organism used by geneticists to investigate gene functions. Children with 16p11.2 CNV also have enlarged or decreased head sizes and suffer from obesity or are underweight.
Interestingly, the RhoA pathway has recently been implicated in a rare form of autism called Timothy syndrome, which is caused by the mutation in a completely different gene. The researchers now hope to target this pathway therapeutically. They are planning to test RhoA pathway inhibitors using a stem cell model of autism.
Based on material originally posted by University of California - San Diego.