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Ypel5 regulates liver development and function in zebrafish.

Yun Deng1,2, Xiao Han1,2, Huiqiao Chen3

  • 1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Journal of Molecular Cell Biology
|March 22, 2023
PubMed
Summary

The Yippee-like 5 (YPEL5) gene is essential for liver function in zebrafish. Loss of YPEL5 causes liver enlargement and metabolic dysfunction, highlighting its role in vertebrate liver health.

Keywords:
HNF4APPARα signalingYPEL5hepatic functionhepatomegaly

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Area of Science:

  • Developmental Biology
  • Genetics
  • Zebrafish Models

Background:

  • The Yippee-like 5 (YPEL5) gene family is conserved across eukaryotes.
  • The physiological role of YPEL5 in vertebrates remains largely uncharacterized due to a lack of genetic models.

Purpose of the Study:

  • To investigate the in vivo function of YPEL5 in vertebrates.
  • To elucidate the molecular mechanisms underlying YPEL5's role in liver physiology.

Main Methods:

  • CRISPR/Cas9 genome editing to generate ypel5 knockout zebrafish.
  • Metabolomic and transcriptomic analyses to assess hepatic function.
  • Gene expression and signaling pathway analysis.

Main Results:

  • ypel5-/- mutant zebrafish exhibit liver enlargement and increased hepatic cell proliferation.
  • Hepatic metabolism and function are significantly dysregulated in ypel5 mutants.
  • Ypel5 positively regulates Hnf4a expression, which is crucial for rescuing hepatic defects. PPARα signaling mediates this regulation.

Conclusions:

  • Ypel5 plays a critical role in regulating hepatocyte proliferation and maintaining liver function in vivo.
  • This study provides the first evidence for the physiological importance of YPEL5 in vertebrate liver development and function.