Decreased cohesin in the brain leads to defective synapse development and anxiety-related behavior

Yuki Fujita, Koji Masuda, Masashige Bando, Ryuichiro Nakato, Yuki Katou, Takashi Tanaka, Masahiro Nakayama, Keizo Takao, Tsuyoshi Miyakawa, Tatsunori Tanaka, Yukio Ago, Hitoshi Hashimoto, Katsuhiko Shirahige, Toshihide Yamashita

研究成果: Article

14 引用 (Scopus)

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Abnormal epigenetic regulation can cause the nervous system to develop abnormally. Here, we sought to understand the mechanism by which this occurs by investigating the protein complex cohesin, which is considered to regulate gene expression and, when defective, is associated with higher-level brain dysfunction and the developmental disorder Cornelia de Lange syndrome (CdLS). We generated conditional Smc3-knockout mice and observed greater dendritic complexity and larger numbers of immature synapses in the cerebral cortex of Smc3+/- mice. Smc3+/- mice also exhibited more anxiety-related behavior, which is a symptom of CdLS. Further, a gene ontology analysis after RNA-sequencing suggested the enrichment of immune processes, particularly the response to interferons, in the Smc3+/- mice. Indeed, fewer synapses formed in their cortical neurons, and this phenotype was rescued by STAT1 knockdown. Thus, low levels of cohesin expression in the developing brain lead to changes in gene expression that in turn lead to a specific and abnormal neuronal and behavioral phenotype.

元の言語English
ページ(範囲)1431-1452
ページ数22
ジャーナルJournal of Experimental Medicine
214
発行部数5
DOI
出版物ステータスPublished - 01-05-2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Fujita, Y., Masuda, K., Bando, M., Nakato, R., Katou, Y., Tanaka, T., Nakayama, M., Takao, K., Miyakawa, T., Tanaka, T., Ago, Y., Hashimoto, H., Shirahige, K., & Yamashita, T. (2017). Decreased cohesin in the brain leads to defective synapse development and anxiety-related behavior. Journal of Experimental Medicine, 214(5), 1431-1452. https://doi.org/10.1084/jem.20161517