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

Zwerts, F; Lupu, F; De Vriese, A; Pollefeyt, S; Moons, L; Altura, RA; ... Conway, EM; + view all (2007) Lack of endothelial cell survivin causes embryonic defects in angiogenesis, cardiogenesis, and neural tube closure. BLOOD , 109 (11) 4742 - 4752. 10.1182/blood-2006-06-028068.

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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 endothellum. This was accomplished by intercrossing survivin(lox/lox) mice with mice expressing cre recombinase under the control of the endothelial cell specific tiel promoter (tiel-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.

Type:Article
Title:Lack of endothelial cell survivin causes embryonic defects in angiogenesis, cardiogenesis, and neural tube closure
DOI:10.1182/blood-2006-06-028068
Keywords:BLOOD-VESSEL DEVELOPMENT, VASCULAR DEVELOPMENT, ENDOCARDIAL CUSHION, TRANSGENIC MICE, DEFICIENT MICE, STEM-CELLS, CARDIOVASCULAR DEVELOPMENT, TRANSCRIPTION FACTOR, APOPTOSIS PROTEIN, UP-REGULATION
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)

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