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Functionally conserved effects of rapamycin exposure on zebrafish.

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Rapamycin treatment impacts gene expression in zebrafish cells, affecting protein synthesis and cellular machinery. Zebrafish and mouse pathways show conserved responses to rapamycin, with dose-dependent effects on embryo growth and pigmentation.

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Comparative Genomics

Background:

  • Mechanistic target of rapamycin (mTOR) is a key regulator of cell growth and proliferation, conserved across species.
  • Rapamycin is a known inhibitor of mTOR, utilized as an anti-cancer and immunosuppressant drug.
  • Zebrafish serve as a valuable model organism for studying conserved biological pathways.

Purpose of the Study:

  • To investigate the transcriptomic effects of rapamycin on zebrafish fibroblast cells (ZF4).
  • To compare rapamycin-modulated pathways in zebrafish with those in mice using meta-analysis.
  • To assess the dose-dependent effects of rapamycin on zebrafish embryo development.

Main Methods:

  • Microarray analysis of ZF4 cells treated with rapamycin.
  • Meta-analysis of heterogeneous mouse rapamycin microarray datasets.
  • Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analysis.
  • Observation of zebrafish embryo body size and pigmentation changes in response to varying rapamycin doses.

Main Results:

  • Rapamycin modulated a wide array of genes in ZF4 cells, including those involved in protein synthesis, mitochondrial and proteasomal function, cell cycle, metabolism, and oxidative phosphorylation.
  • A coordinated reduction in proteasomal and mitochondrial ribosomal subunits was observed, alongside an increase in other ribosomal subunits.
  • Functional pathway analysis revealed significant conservation in rapamycin responses between zebrafish and mice.
  • Zebrafish embryos exhibited a dose-dependent decrease in body size and pigmentation upon rapamycin exposure.

Conclusions:

  • The study demonstrates conserved functional pathways modulated by rapamycin between zebrafish and mice at the transcriptomic level.
  • Rapamycin significantly impacts cellular processes related to growth and metabolism in zebrafish.
  • Rapamycin exposure causes dose-dependent developmental effects in zebrafish embryos, highlighting its impact on growth and pigmentation.