2015 Fiscal Year Final Research Report
Functional analysis of MDGA family proteins on neural circuit formation of cerebral cortex.
| Project/Area Number |
25460059
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Research Collaborator |
Craig Ann Marie The University of British Columbia, Neurobiology Research Centre, Professor & Canada Research Chair
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 自閉症スペクトラム障害 / 統合失調症 / MDGA1 / MDGA2 / Neuroligin / シナプス形成 / Ｅ/Ｉバランス |
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| Outline of Final Research Achievements |
Mdga1 encodes a GPI-anchored IgSF protein, which we isolated as a gene expressed by a specific subset of neurons. In mouse coticogenesis, Mdga1 is selectively expressed by the upper layer neurons, while the other family member Mdga2 is widely expressed in a brain. We previously showed that Mdga1 is required for proper radial migration of a subset of upper-layer neurons; however, the resultant layer structure becomes apparently normal. We further investigated the function of MDGA family proteins in postnatal brain function since expression of Mdga1/2 persists throughput the life. It was shown that MDGA1/2 directly interact with Neuroligin family molecules to inhibit their binding to Neurexin, and we found that MDGA1 deficient mice showed more inhibitory synapses and MDGA2 +/- mice showed more excitatory synapses in their cortexes to exhibit behavioral abnormality related to schizophrenia or ASD, suggesting that MDGAs play an important role for maintaining proper E/I balance in a brain.
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| Free Research Field |
神経科学
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