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Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish

Author

Listed:
  • Shaoyang Zhao

    (University of Science and Technology of China
    Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Jianhong Xia

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Xiuhua Wu

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Leilei Zhang

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Pengtao Wang

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Haiyun Wang

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Heying Li

    (Chinese Academy of Sciences)

  • Xiaoshan Wang

    (Chinese Academy of Sciences)

  • Yan Chen

    (Chinese Academy of Sciences)

  • Jean Agnetti

    (Chinese Academy of Sciences)

  • Yinxiong Li

    (Chinese Academy of Sciences)

  • Duanqing Pei

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Xiaodong Shu

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

Abstract

The class III PI3-kinase (PIK3C3) is an enzyme responsible for the generation of phosphatidylinositol 3-phosphate (PI3P), a critical component of vesicular membrane. Here, we report that PIK3C3 deficiency in zebrafish results in intestinal injury and inflammation. In pik3c3 mutants, gut tube forms but fails to be maintained. Gene expression analysis reveals that barrier-function-related inflammatory bowel disease (IBD) susceptibility genes (e-cadherin, hnf4a, ttc7a) are suppressed, while inflammatory response genes are stimulated in the mutants. Histological analysis shows neutrophil infiltration into mutant intestinal epithelium and the clearance of gut microbiota. Yet, gut microorganisms appear dispensable as mutants cultured under germ-free condition have similar intestinal defects. Mechanistically, we show that PIK3C3 deficiency suppresses the formation of PI3P and disrupts the polarized distribution of cell-junction proteins in intestinal epithelial cells. These results not only reveal a role of PIK3C3 in gut homeostasis, but also provide a zebrafish IBD model.

Suggested Citation

  • Shaoyang Zhao & Jianhong Xia & Xiuhua Wu & Leilei Zhang & Pengtao Wang & Haiyun Wang & Heying Li & Xiaoshan Wang & Yan Chen & Jean Agnetti & Yinxiong Li & Duanqing Pei & Xiaodong Shu, 2018. "Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05105-8
    DOI: 10.1038/s41467-018-05105-8
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