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 language | English |
|---|---|
| Pages (from-to) | 4742-4752 |
| Number of pages | 11 |
| Journal | Blood |
| Volume | 109 |
| Issue number | 11 |
| DOIs | |
| State | Published - Jun 1 2007 |
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ASJC Scopus subject areas
- Hematology
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Lack of endothelial cell survivin causes embryonic defects in angiogenesis, cardiogenesis, and neural tube closure. / Zwerts, Femke; Lupu, Florea; De Vriese, Astrid; Pollefeyt, Saskia; Moons, Lieve; Altura, Rachel A.; Jiang, Yuying; Maxwell, Patrick H.; Hill, Peter; Oh, Hideyasu; Rieker, Claus; Collen, Désiré; Conway, Simon; Conway, Edward M.
In: Blood, Vol. 109, No. 11, 01.06.2007, p. 4742-4752.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lack of endothelial cell survivin causes embryonic defects in angiogenesis, cardiogenesis, and neural tube closure
AU - Zwerts, Femke
AU - Lupu, Florea
AU - De Vriese, Astrid
AU - Pollefeyt, Saskia
AU - Moons, Lieve
AU - Altura, Rachel A.
AU - Jiang, Yuying
AU - Maxwell, Patrick H.
AU - Hill, Peter
AU - Oh, Hideyasu
AU - Rieker, Claus
AU - Collen, Désiré
AU - Conway, Simon
AU - Conway, Edward M.
PY - 2007/6/1
Y1 - 2007/6/1
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2006-06-028068
DO - 10.1182/blood-2006-06-028068
M3 - Article
VL - 109
SP - 4742
EP - 4752
JO - Blood
JF - Blood
SN - 0006-4971
IS - 11
ER -