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XB-ART-37713
Development June 1, 2008; 135 (11): 1903-11.

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

Rodrigues CO , Nerlick ST , White EL , Cleveland JL , King ML .


Abstract
Myc-deficient mice fail to develop normal vascular networks and Myc-deficient embryonic stem cells fail to provoke a tumor angiogenic response when injected into immune compromised mice. However, the molecular underpinnings of these defects are poorly understood. To assess whether Myc indeed contributes to embryonic vasculogenesis we evaluated Myc function in Xenopus laevis embryogenesis. Here, we report that Xc-Myc is required for the normal assembly of endothelial cells into patent vessels during both angiogenesis and lymphangiogenesis. Accordingly, the specific knockdown of Xc-Myc provokes massive embryonic edema and hemorrhage. Conversely, Xc-Myc overexpression triggers the formation of ectopic vascular beds in embryos. Myc is required for normal expression of Slug/Snail2 and Twist, and either XSlug/Snail2 or XTwist could compensate for defects manifest by Xc-Myc knockdown. Importantly, knockdown of Xc-Myc, XSlug/Snail2 or XTwist within the lateral plate mesoderm, but not the neural crest, provoked embryonic edema and hemorrhage. Collectively, these findings support a model in which Myc, Twist and Slug/Snail2 function in a regulatory circuit within lateral plate mesoderm that directs normal vessel formation in both the vascular and lymphatic systems.

PubMed ID: 18469221
PMC ID: PMC2741485
Article link: Development
Grant support: [+]

Species referenced: Xenopus
Genes referenced: aplnr erg mmut myc prox1 snai2 tal1 twist1
Morpholinos: myc MO1 snai2 MO3 twist1 MO3


Article Images: [+] show captions
References [+] :
Baudino, c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression. 2002, Pubmed