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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

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Gene-Environment Interactions Target Mitogen-activated Protein 3 Kinase 1 (MAP3K1) Signaling in Eyelid Morphogenesis

Maureen Mongan1, Qinghang Meng1, Jingjing Wang1

  • 1From the Departments of Environmental Health and.

The Journal of Biological Chemistry
|June 26, 2015
PubMed

Insights

Environmental pollutants like dioxins can interact with genetic mutations to disrupt fetal development. This study shows dioxin exposure blocks embryonic eyelid closure in mice with weakened MAP3K1 signaling, highlighting a key gene-environment interaction.

Area of Science:

  • Developmental Biology
  • Environmental Toxicology
  • Molecular Genetics

Background:

  • Gene-environment interactions are crucial for biological outcomes but their mechanisms remain unclear.
  • Mouse embryonic eyelid closure serves as a model for studying genetic control of development.
  • Understanding how environmental pollutants influence genetic risk for developmental abnormalities is critical.

Purpose of the Study:

  • To investigate the impact of dioxin-like environmental pollutants on genetic risk for developmental abnormalities.
  • To identify key signaling pathways involved in gene-environment interactions during development.
  • To elucidate the role of mitogen-activated protein 3 kinase 1 (MAP3K1) signaling in dioxin-induced developmental disruption.

Main Methods:

  • Utilized a mouse model of embryonic eyelid closure.
  • Exposed genetically modified mice with varying signaling pathway attenuations (MAP3K1, EGFR, WNT) to dioxin-like pollutants.
  • Assessed the effects of exposure on eyelid closure and c-Jun phosphorylation in embryonic eyelid epithelium.

Main Results:

  • Dioxin exposure blocked embryonic eyelid closure in mice with attenuated MAP3K1 signaling, but not in wild-type or mice with attenuated EGFR or WNT signaling.
  • Dioxin exposure inhibited c-Jun phosphorylation in Map3k1(+/-) embryonic eyelid epithelium.
  • MAP3K1 signaling acts as a focal point for gene-environment cross-talk, where dioxin-induced aryl hydrocarbon receptor (AHR) pathways synergize with gene mutations.

Conclusions:

  • A novel mechanism reveals how the dioxin-AHR axis interacts with MAP3K1 signaling pathways during fetal development.
  • Specific genetic alterations can heighten the risk of developmental abnormalities resulting from environmental pollutant exposure.
  • This research provides empirical evidence for gene-environment interactions influencing developmental outcomes.
Keywords:
aryl hydrocarbon receptor (AhR) (AHR)c-Jun N-terminal kinase (JNK)dioxinembryonic eyelid closuregene-environment interactionmitogen-activated protein 3 kinase 1 (MAP3K1)morphogenesissignaling

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