A developmental pathway responsible for schizophrenia?

A paper published this month in ‘Schizophrenia Research’ claims to have pinpointed the gestational pathway, which, when disrupted, causes the development of schizophrenia later in life.

The team, led by Dr. Michal Stachowiak at the University of Buffalo, developed a mouse model which they claim accurately mimics the symptoms of schizophrenia by mutating the Fibroblast Growth Factor Receptor (FGFR1) protein.  Schizophrenia is a debilitating mental illness which has a highly complex pathology and Stachowiak et al. propose that their disruption of Integrative Nuclear FGFR1 Signalling (INFS) explains why such heterogeneous patterns of gene mutation are seen in different individuals with the disorder.

The research aimed to resolve how such a wide variety of genes have been implicated in schizophrenia by proposing the role of a central integrating pathway.  INFS is a point of integration for neurodevelopmental pathways controlling progenitor development; it is an intersection of up to 160 gene expression pathways. Initially FGFR1, the protein mutated in the mice, was shown by the Buffalo group to bind some of the implicated genes in embryonic stem cells.

Subsequently, mutant FGFR1 mice were created, with the knock-out targeting the dopaminergic neurons of the substantia nigra pars compacta and the ventral tegmental area. The mice were then studied for pathology that mimics that of schizophrenia and appear to exhibit altered brain anatomy, neurochemistry and behaviour, thereby reflecting the human disorder.

This model does offer an explanation for the idiosyncrasy in the mutations found between people with the illness as it is postulated that mutations in elements that feed into the INFS pathway could destabilize it. The authors of the paper suggest that this INFS pathway hints at a new target in the efforts to prevent the development of schizophrenia. However, it is also difficult to accurately assess the true degree to which any animal model can successfully simulate a complex human disorder.

About Aishling Cooke

Aishling is a second year undergraduate studying Biomedical Science at St Anne's.