Is the FOXG1 gene the cause of autism?

Macrocephaly is a proportional enlargement of the brain, often found in children with severe autism spectrum disorder (ASD). The disease is inevitably accompanied by mental retardation and in many cases leads to sudden death. Until now, the causes of various pathologies associated with ASD and the ways to treat them remain unknown. But recent studies of genetic mutations in rare forms of the disease have shown that disorders begin with improper brain development in the embryo.

Flora Vaccarino from Yale University and her colleagues tried to find deviations in the formation of the cerebral cortex, informs news.еizvestia.com .

To do this, they extracted stem cells from the skin of four children with macrocephaly, as well as from their parents who do not suffer from the disease. The cells were then reprogrammed chemically and made to turn into tiny three-dimensional structures that mimic the developing human forebrain.

As reported in an article published in Cell (Mariani et al., FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders – VM), miniature organs grown from cells of patients with ASD and healthy people looked different. Scientists compared the level of gene expression, and found in the first case increased activity of genes that control the growth of brain cells. As a result, the children's cells divided faster and formed more inhibitory neurons and synapses, which, in turn, suppressed other cell types.

"Disorders such as accelerated cell division, overproduction of inhibitory neurons, and an excessive number of synapses may be precursors of those abnormalities in brain development found in children with severe forms of ASD," Vaccarino says in a university press release (Making 'miniature brains' from skin cells to better understand autism – VM).

In particular, the researchers registered a tenfold increase in the activity of the FOXG1 gene, which plays an important role in the growth of neurons at the stage of early embryonic development. With the help of modern molecular technologies, they corrected the overexpression of the gene and managed to reverse some negative neurobiological changes.

"By regulating the expression level of FOXG1, we were able to prevent the overproduction of inhibitory neurons from the patient's cells,– explains Vaccarino. "It is noteworthy that we also found a link between changes in the expression of this gene and the severity of macrocephaly and autism in the patient."

Scientists say that, despite the small number of people surveyed, the results of their work provide the basis for further study of the normal development of the human brain and various abnormalities, including autism spectrum disorders. 

For example, the FOXG1 gene can be used as a biomarker of severe forms of the disease and become a potential target for new drugs.

Portal "Eternal youth" http://vechnayamolodost.ru

20.07.2015