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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1431-1452
Number of pages22
JournalJournal of Experimental Medicine
Volume214
Issue number5
DOIs
Publication statusPublished - 01-05-2017

Fingerprint

De Lange Syndrome
Synapses
Anxiety
Brain
RNA Sequence Analysis
Phenotype
Gene Expression
Gene Ontology
Epigenomics
Knockout Mice
Cerebral Cortex
Interferons
Nervous System
Neurons
cohesins

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Fujita, Y., Masuda, K., Bando, M., Nakato, R., Katou, Y., Tanaka, T., ... 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
Fujita, Yuki ; Masuda, Koji ; Bando, Masashige ; Nakato, Ryuichiro ; Katou, Yuki ; Tanaka, Takashi ; Nakayama, Masahiro ; Takao, Keizo ; Miyakawa, Tsuyoshi ; Tanaka, Tatsunori ; Ago, Yukio ; Hashimoto, Hitoshi ; Shirahige, Katsuhiko ; Yamashita, Toshihide. / Decreased cohesin in the brain leads to defective synapse development and anxiety-related behavior. In: Journal of Experimental Medicine. 2017 ; Vol. 214, No. 5. pp. 1431-1452.
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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, vol. 214, no. 5, pp. 1431-1452. https://doi.org/10.1084/jem.20161517

Decreased cohesin in the brain leads to defective synapse development and anxiety-related behavior. / Fujita, Yuki; Masuda, Koji; Bando, Masashige; Nakato, Ryuichiro; Katou, Yuki; Tanaka, Takashi; Nakayama, Masahiro; Takao, Keizo; Miyakawa, Tsuyoshi; Tanaka, Tatsunori; Ago, Yukio; Hashimoto, Hitoshi; Shirahige, Katsuhiko; Yamashita, Toshihide.

In: Journal of Experimental Medicine, Vol. 214, No. 5, 01.05.2017, p. 1431-1452.

Research output: Contribution to journalArticle

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AU - Fujita, Yuki

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AU - Katou, Yuki

AU - Tanaka, Takashi

AU - Nakayama, Masahiro

AU - Takao, Keizo

AU - Miyakawa, Tsuyoshi

AU - Tanaka, Tatsunori

AU - Ago, Yukio

AU - Hashimoto, Hitoshi

AU - Shirahige, Katsuhiko

AU - Yamashita, Toshihide

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