July 19, 2018
Nagoya University
Keio University School of Medicine
Japan Agency for Medical Research and Development
A research group led by Professor Norio Ozaki of the Department of Psychiatry and Child and Adolescent Psychiatry, Nagoya University Graduate School of Medicine (Dean: Kenji Kadomatsu); Project Assistant Professor Yuko Arioka of the Center for Advanced Medicine and Clinical Research, Nagoya University Hospital (Director: Naoki Ishiguro); and Project Associate Professor Daisuke Mori of the Brain and Mind Research Center has revealed that a reelin gene variant, identified in patients with schizophrenia, disrupts the stability of neuronal migration, a crucial process in brain morphogenesis. This was discovered using human iPS cells. The study was conducted in collaboration with the research group of Professor Hideyuki Okano of the Keio University School of Medicine.
For the brain to function correctly, neurons must migrate properly from their birthplace to their destination, allowing the brain to form normally. One of the molecules that controls this neuronal migration is a protein called reelin, which is encoded by the reelin gene. Previous genomic studies have suggested that variants of the reelin gene are involved in the onset of psychiatric disorders such as schizophrenia. However, it was unclear how these reelin gene variants affect human neurons in the brain and lead to the development of psychiatric disorders. In this study, the research group generated iPS cells from a schizophrenia patient with a reelin gene variant and also created iPS cells with an artificially introduced reelin gene variant using genome editing technology. By differentiating these two types of iPS cells into uniform dopaminergic neurons and examining the migration trajectory of individual cells, they found that while normal dopaminergic neurons migrate with consistent directionality, those with the reelin gene variant exhibit unstable and erratic movement. These findings not only clarify the impact of reelin gene variants on human neurons but also hold promise for application in developing treatments for psychiatric disorders by normalizing this effect (the instability of neuronal migration directionality).
This research was published in the online edition of the international scientific journal "Translational Psychiatry" on July 19, 2018 (9:00 a.m. JST).
For the full press release, please see below.