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| Normal human neural stem cells (left) and neural stem cells with a 15q11.2 deletion, a risk factor for schizophrenia (right)--Courtesy of Ki-Jun Yoon/Johns Hopkins Medicine |
In an effort to better understand the risk factors of schizophrenia, Johns Hopkins researchers have found how a genetic abnormality associated with the mental disorder alters brain cell development.
In the journal Cell Stem Cell, researchers found that the loss of a particular gene alters the framework of developing brain cells, disrupting the orderly way in which those cells would normally form layers.
No single genetic mutation is known to cause schizophrenia. Instead, genomewide association studies have pinpointed variations that are more common in people with the condition than in the general population--including one part of the genome, called 15q11.2.
In the new study, researchers took skin cells from people with schizophrenia who were missing part of 15q11.2 on one of their chromosomes. Investigators grew the human skin cells in a dish and coaxed them to become induced pluripotent stem cells, and then into neural progenitor cells, a kind of stem cell found in the developing brain.
Neural progenitors form orderly rings when grown in a dish, but those with the deleted section of 15q11.2 did not. This led researchers to determine which gene in the missing part of the genome caused the abnormal cell layers gene. They zeroed in on a gene called CYFIP1, and to test their theory, they altered the genomes of neural progenitors in mouse embryos so that they made less of the protein created by CYFIP1.
When examining the brain cells of fetal mice, researchers found that they had similar defects in structure to those in the dish-grown human cells.
The team believes the study may also help investigate other mental illnesses.
"Using induced pluripotent stem cells from people with schizophrenia allowed us to see how their genes affected brain development," Johns Hopkins neurology and neuroscience professor and study author Hongjun Song said in a statement. "Next, we'd like to investigate what effects remain in the mature brain."
- see the study abstract
- read the press release