| 1 | Mol Brain 2016 -1 9: 54 |
|---|---|
| PMID | 27189492 |
| Title | Growth arrest specific gene 7 is associated with schizophrenia and regulates neuronal migration and morphogenesis. |
| Abstract | schizophreniais a highly heritable chronic mental disorder with significant abnormalities in brain function. The neurodevelopmental hypothesis proposes thatschizophreniaoriginates in the prenatal period due to impairments in neuronal developmental processes such as migration and arborization, leading to abnormal brain maturation. Previous studies have identified multiple promising candidate genes that drive functions in neurodevelopment and are associated withschizophrenia. However, the molecular mechanisms of how they exert effects on the pathophysiology ofschizophreniaremain largely unknown. In our research, we identified growth arrest specific gene 7 (GAS7) as aschizophrenia在两个独立的风险基因Han Chinese populations using a two-stage association study. Functional experiments were done to further explore the underlying mechanisms of the role ofGAS7in cortical development. In vitro, we discovered thatGAS7contributed to neurite outgrowth through the F-BAR domain. In vivo, overexpression ofGAS7arrested neuronal migration by increasing leading process branching, while suppression ofGAS7could inhibit neuronal migration by lengthening leading processes. Through a series of behavioral tests, we also found thatGAS7-deficient mice showed sensorimotor gating deficits. Our results demonstrateGAS7as a susceptibility gene forschizophrenia.GAS7might participate in the pathogenesis ofschizophreniaby regulating neurite outgrowth and neuronal migration through its C-terminal F-BAR domain. The impaired pre-pulse inhibition (PPI) ofGAS7-deficient mice might mirror the disease-related behavior inschizophrenia. |
| SCZ Keywords | schizophrenia |