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Related Experiment Videos

Mekk3 is essential for early embryonic cardiovascular development.

J Yang1, M Boerm, M McCarty

  • 1Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.

Nature Genetics
|March 4, 2000
PubMed
Summary

Mekk3 (Map3k3) is essential for embryonic blood vessel development, including vasculogenesis and angiogenesis. Its absence disrupts yolk sac integrity and blocks angiogenesis, highlighting its critical role in vascular formation.

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Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Blood vessel formation involves vasculogenesis and angiogenesis, regulated by complex molecular pathways.
  • Intracellular signal transduction in these processes remains incompletely understood.

Purpose of the Study:

  • To investigate the role of Map3k3 (Mekk3) in embryonic blood vessel development.
  • To elucidate the intracellular signaling pathways Mekk3 participates in during vascular formation.

Main Methods:

  • Gene disruption of Map3k3 in mouse models (Map3k3-/-).
  • Analysis of embryonic development, yolk sac integrity, and blood vessel formation.
  • Assessment of gene expression for key angiogenic factors (Vegf-1, angiopoietin) and their receptors.

Related Experiment Videos

  • Investigation of Mekk3's downstream targets, including Mef2c, via the p38 MAPK cascade.

    • Main Results:

    • Map3k3-/- embryos exhibited embryonic lethality around E11 with severe defects in blood vessel development and yolk sac structure.
    • Angiogenesis was significantly impaired, arrested around E9.5 in mutant embryos.
    • Mekk3 deficiency did not affect Vegf-1 or angiopoietin signaling pathways.
    • Embryonic but not maternal blood vessel development in the placenta was compromised, indicating intrinsic endothelial cell defects.
    • Mekk3 was found to activate Mef2c through the p38 MAPK pathway.

    Conclusions:

    • Mekk3 is indispensable for embryonic blood vessel development, impacting both vasculogenesis and angiogenesis.
    • The Mekk3-Mef2c pathway, mediated by p38 MAPK, is crucial for early cardiovascular development.
    • Mekk3 represents a potential therapeutic target for modulating angiogenesis in various conditions.