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Trim69 regulates zebrafish brain development by ap-1 pathway.

Ruiqin Han1, Renxian Wang1, Qing Zhao1

  • 1National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.

Scientific Reports
|April 7, 2016
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Summary

The TRIM69 protein is crucial for zebrafish brain development and neurogenesis. Its knockdown causes brain deformities and apoptosis, a process linked to the c-Jun/AP-1 pathway.

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Area of Science:

  • Developmental Biology
  • Neuroscience
  • Molecular Biology

Background:

  • The TRIM (Tripartite Motif) protein family plays diverse roles in cellular functions, including apoptosis, differentiation, neurogenesis, and immune responses.
  • Trim69, a novel gene identified in humans, has a homologous counterpart in zebrafish, suggesting conserved functions.

Purpose of the Study:

  • To investigate the function of trim69 in zebrafish neurogenesis and brain development.
  • To elucidate the molecular mechanisms underlying trim69's role in the developing brain.

Main Methods:

  • Zebrafish model system utilized for studying neurogenesis.
  • Trim69 gene knockdown using morpholino technology.
  • Analysis of brain development, apoptosis, and expression of neuronal markers.
  • Human cell line experiments to investigate protein interactions and pathway analysis.
  • Rescue experiments involving human TRIM69 mRNA co-injection and dual knockdown of trim69 and c-Jun.

Main Results:

  • Trim69 is expressed in the early stages of zebrafish embryonic brain development.
  • Knockdown of trim69 resulted in significant brain malformations, increased apoptosis in the head, and reduced expression of neuronal differentiation and stem cell markers.
  • The observed phenotype was rescued by co-expressing human TRIM69 mRNA.
  • TRIM69 interacts with c-Jun, with TRIM69 knockdown increasing c-Jun expression and TRIM69 overexpression decreasing it.
  • Simultaneous knockdown of both trim69 and c-Jun rescued the brain defects and molecular phenotypes.

Conclusions:

  • Trim69 plays a critical role in regulating zebrafish brain development and neurogenesis.
  • The function of trim69 in brain development is mediated through the c-Jun/AP-1 signaling pathway.