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Aplnra/b Sequentially Regulate Organ Left-Right Patterning via Distinct Mechanisms.

Chengke Zhu1,2, Zhenghua Guo3, Yu Zhang4

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Summary

The APJ receptor (APJ/Aplnr) and its ligands (apela/apln) are crucial for zebrafish organ left-right patterning. Distinct roles of APJ receptor subtypes and ligands coordinate development through mechanisms like KV/cilia morphogenesis.

Keywords:
apela/aplnaplnra/bleft right patterningmidlinespaw

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Area of Science:

  • Developmental Biology
  • Genetics
  • Molecular Biology

Background:

  • The G protein-coupled receptor APJ/Aplnr is known for roles in cardiovascular development.
  • Its involvement in organ left-right (LR) patterning remains largely uncharacterized.

Purpose of the Study:

  • To investigate the role of APJ/Aplnr and its ligands in organ LR patterning in zebrafish.
  • To elucidate the distinct mechanisms and developmental stages involved.

Main Methods:

  • Utilized zebrafish as a model organism.
  • Performed loss-of-function studies for aplnra/b and analyzed downstream effects on organ asymmetry.
  • Investigated the roles of apela and apln as endogenous ligands.
  • Examined gene expression patterns, including Nodal/spaw, foxj1a, fgf8, dnh9, and lft1.
  • Assessed KV/cilia morphogenesis.

Main Results:

  • Loss of aplnra/b in zebrafish caused heart and liver LR asymmetry defects.
  • These defects were associated with disturbed KV/cilia morphogenesis and disrupted left-sided Nodal/spaw expression.
  • Only aplnra loss of function affected KV/cilia morphogenesis.
  • Apela acted as the early ligand regulating KV morphogenesis and subsequent Nodal/spaw expression.
  • The aplnra-apela cascade enhanced foxj1a expression during KV development.
  • At later stages, aplnra/b contributed to trunk midline lft1 expression, potentially mediated by both apela and apln.

Conclusions:

  • This study identifies a novel role for APJ/Aplnr and its ligands apela/apln in zebrafish organ LR patterning.
  • Distinct roles of aplnra-apela and aplnra/b-apela/apln were clarified in orchestrating organ LR patterning at different developmental stages.