A Myc-Slug (Snail2)/Twist regulatory circuit directs vascular development

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Claudia O Rodrigues1, Steve T Nerlick, Elsie L White

  • 1Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN 38105, USA.

Development (Cambridge, England)
|May 13, 2008
PubMed

Insights

Myc is crucial for forming blood and lymphatic vessels during embryonic development. Its regulation of Twist and Slug/Snail2 ensures proper vascular network assembly, preventing embryonic edema and hemorrhage.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Vascular Biology

Background:

  • Myc-deficient mice exhibit impaired vascular network formation and angiogenic responses.
  • The precise role of Myc in embryonic vasculogenesis remains unclear.
  • Understanding Myc's function is vital for comprehending vascular development.

Purpose of the Study:

  • To investigate the role of Myc in embryonic vasculogenesis using Xenopus laevis.
  • To elucidate the molecular mechanisms by which Myc influences vessel formation.
  • To determine if Myc interacts with other key developmental genes in this process.

Main Methods:

  • Knockdown and overexpression of Xc-Myc in Xenopus embryos.
  • Assessment of vascular and lymphatic vessel development.
  • Analysis of gene expression for key developmental regulators like Slug/Snail2 and Twist.
  • Localization studies of gene function within embryonic tissues.

Main Results:

  • Xc-Myc is essential for the proper assembly of endothelial cells into patent vessels.
  • Xc-Myc knockdown leads to embryonic edema and hemorrhage.
  • Xc-Myc overexpression results in ectopic vascular bed formation.
  • Myc regulates the expression of XSlug/Snail2 and XTwist, which can compensate for Xc-Myc loss.
  • The critical function of Myc, Slug/Snail2, and Twist in vessel formation resides in the lateral plate mesoderm.

Conclusions:

  • Myc is a key regulator of both angiogenesis and lymphangiogenesis.
  • A regulatory circuit involving Myc, Twist, and Slug/Snail2 in the lateral plate mesoderm directs normal vascular and lymphatic system development.
  • These findings provide insights into the molecular basis of vascular development and associated congenital defects.

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