Lack of endothelial cell survivin causes embryonic defects in angiogenesis, cardiogenesis, and neural tube closure

Femke Zwerts, Florea Lupu, Astrid De Vriese, Saskia Pollefeyt, Lieve Moons, Rachel A. Altura, Yuying Jiang, Patrick H. Maxwell, Peter Hill, Hideyasu Oh, Claus Rieker, Désiré Collen, Simon J. Conway, Edward M. Conway

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

We explored the physiologic role of endothelial cell apoptosis during development by generating mouse embryos lacking the inhibitor of apoptosis protein (IAP) survivin in endothelium. This was accomplished by intercrossing survivinlox/lox mice with mice expressing cre recombinase under the control of the endothelial cell specific tie1 promoter (tie1-cre mice). Lack of endothelial cell survivin resulted in embryonic lethality. Mutant embryos had prominent and diffuse hemorrhages from embryonic day 9.5 (E9.5) and died before E13.5. Heart development was strikingly abnormal. Survivin-null endocardial lineage cells could not support normal epithelial-mesenchymal transformation (EMT), resulting in hypoplastic endocardial cushions and in utero heart failure. In addition, 30% of mutant embryos had neural tube closure defects (NTDs) that were not caused by bleeding or growth retardation, but were likely due to alterations in the release of soluble factors from endothelial cells that otherwise support neural stem cell proliferation and neurulation. Thus, regulation of endothelial cell survival, and maintenance of vascular integrity by survivin are crucial for normal embryonic angiogenesis, cardiogenesis, and neurogenesis.

Original languageEnglish (US)
Pages (from-to)4742-4752
Number of pages11
JournalBlood
Volume109
Issue number11
DOIs
StatePublished - Jun 1 2007

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Zwerts, F., Lupu, F., De Vriese, A., Pollefeyt, S., Moons, L., Altura, R. A., Jiang, Y., Maxwell, P. H., Hill, P., Oh, H., Rieker, C., Collen, D., Conway, S. J., & Conway, E. M. (2007). Lack of endothelial cell survivin causes embryonic defects in angiogenesis, cardiogenesis, and neural tube closure. Blood, 109(11), 4742-4752. https://doi.org/10.1182/blood-2006-06-028068