Mutations in the scaffolding protein disrupted in schizophrenia 1 (DISC1) have been linked to schizophrenia and other psychiatric diseases. Now, Eunchai Kang et al. report that the interaction between DISC1 and fasciculation and elongation protein zeta-1 (FEZ1) modulates neuronal development in mice (Neuron 72, 559–571).

The researchers found that knocking down FEZ1 expression in mouse hippocampus led to the generation of neurons with more complex dendrites, which is similar to the phenotype observed when DISC1 is knocked down in mice. When they infused a peptide that would block the DISC1-FEZ1 interaction, Kang and colleagues also observed an increase in dendritic complexity, suggesting that this interaction is necessary to maintain normal development of neurons in the hippocampus, a brain structure involved in learning and memory.

Individuals with a particular DISC1 mutation (S704C) have an increased risk of developing schizophrenia. By examining two separate case-control populations, the researchers found that FEZ1 polymorphisms can increase the risk for schizophrenia in individuals who are homozygous for serine at this site in DISC1. However, further work is needed to determine the mechanism behind this observation.