A gene associated with schizophrenia influences a critical stage of early brain development in mice.
Researchers investigated a gene called ZFN804A; one of over 100 identified by a previous study as being linked to schizophrenia risk. ZFN804A is known to be significantly associated with schizophrenia, said Dr Yingwei Mao at Pennsylvania State University, and lead author of the current study.
'We provide molecular evidence showing that ZNF804A could contribute to psychiatric disorders like schizophrenia,' he said. The study supports the idea that early changes in neurodevelopment may trigger effects that are not seen till later in life. Schizophrenia usually manifests in late adolescence or early adulthood.
The researchers demonstrated that ZFN804A is necessary for the development of normal brain structure and function in mouse embryos. The gene influenced two crucial processes: proliferation, which is the replication of neuronal stem cells and migration, which is the movement of neuronal cells to specific locations within the developing brain.
'Disturbances to these processes may cause neuronal stem cells to develop into different types of cells or may cause neurons to migrate to different locations in the brain, changing neuronal circuitry and potentially leading to behavioural disorders like schizophrenia,' explained Dr Mao.
Using a yeast cell model, ZFN804A was also found to interact with at least nine genes that are involved in translating mRNA (messenger RNA) into proteins. This indicates that ZFN804A plays an important role in regulating the decoding of genes to proteins.
The researchers add that ZFN804A also interacts with other genes implicated in schizophrenia risk, highlighting the complexity of schizophrenia and the need to gain a better understanding of the underlying causes.
'Determining the role of ZNF804A is the first step in understanding how schizophrenia-associated genes contribute to abnormal brain development,' said Dr Mao. 'Understanding how these genes interact to contribute to the development of schizophrenia may allow us to identify the general pathway of the disease, potentially providing a better target for treatment.'
The study was published in Molecular Psychiatry.