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First published online May 9, 2008
doi: 10.1242/10.1242/dev.011296

Development 135, 1903-1911 (2008)
Published by The Company of Biologists 2008
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A Myc-Slug (Snail2)/Twist regulatory circuit directs vascular development

Claudia O. Rodrigues1,2, Steve T. Nerlick3, Elsie L. White1, John L. Cleveland1,4,* and Mary Lou King3,*

1 Department of Biochemistry, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
2 Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA.
3 Department of Cell Biology, University of Miami Miller School of Medicine, Miami, FL, USA.
4 Department of Cancer Biology, The Scripps Research Institute-Florida, Jupiter, FL 33458, USA.

* Authors for correspondence (e-mails: jcleve{at}scripps.edu; mking{at}med.miami.edu)

Accepted 26 March 2008

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.

Key words: Myc, Slug/Snail2, Twist, Vasculogenesis, Lymphangiogenesis, Xenopus






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