Commentary Cellscience Reviews Vol 4 No 3 ISSN 1742-8130

Neuregulin-1-induced cell migration:
a neurodevelopmental mechanism for schizophrenia susceptibility?

A series of genetic mapping, gene expression and animal studies implicate Neuregulin 1 (NRG1)-mediated signalling in the neuropathogenesis of the brain disorder schizophrenia (SZ). Understanding the molecular disease pathways involved is a major research focus in SZ. A recent report by Sei and colleagues (2007) identifies an interesting method of investigating the role of the NRG1 gene in vivo using transformed B lymphoblasts from patients with SZ. The authors identify an NRG1-ErbB signaling system analogous to that observed in neuronal cells. NRG1 gene plays critical roles involving many aspects of neurodevelopment and this study focusses on a readily measurable phenotype, cell migration. This is of interest as a substantial, if contraversial, literature suggests that early defects in cell migration may be relevant to SZ susceptibility. The authors report a significantly reduced chemotactic response to NRG1 signaling in SZ. Furthermore, this response is associated with a previously identified and putatively functional risk variant at the gene. Exploratory analyses suggest a main effect and interaction with another functional risk variant (the Val/Met polymorphism) at COMT. This approach is promising for the investigation of other putative SZ risk variants, in particular, the molecular pathway genes involving erbB-NRG1 signaling implicated in SZ susceptibility.

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