Cohesin regulates synapse formation in the brain

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18364
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Osaka University
• Principal Investigator: Fujita Yuki 大阪大学, 医学系研究科, 助教 (60631215)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 中枢神経 / ゲノム

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.

Free Research Field

神経科学