| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Outline of Final Research Achievements |
Cohesin complex is composed of four subunits, Smc3, Smc1, Scc3, and Scc1/Rad21, and has a role in sister chromatid cohesion, which is crucial for accurate chromosome segregation. Cohesin is also known to be involved in chromatin organization by forming chromatin loops at particular loci and regulates gene expression in postmitotic cells.
To investigate the potential role of cohesin in terminally differentiated cells in vivo, we generated conditional Smc3-knockout mice. We observed increased dendritic complexity and decreased spine density in cortical neurons of heterozygous Smc3-knockout mice. Neuron-specific Smc3-knockout mice showed the same phenotype. Heterozygous Smc3-knockout mice exhibited increased anxiety-related behavior, a symptom of Cornelia de Lange syndrome, also caused by disruption of cohesin. Thus, neuronal cohesin contributes to neural network formation, presumably by modulating gene expression, and cohesin deficiency leads to higher brain dysfunction.
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