Determination of hypoxic region by hypoxia marker in developing mouse embryos in vivo: a possible signal for vessel development.
Hypoxia is a well-known signal for angiogenesis, but the recent proposal that hypoxia exists in developing embryonic tissues and that it induces vascular development remains to be proven. In the present study, we demonstrate the presence of hypoxia in normal developing embryos by means of a hypoxia marker, pimonidazole, and its associated antibody. Our data clearly show that hypoxia marker immunoreactivity was highly detected in developing neural tubes, heart, and intersomitic mesenchyme at an early stage of organogenesis, suggesting that hypoxia may exist in the early stages of embryo development. We also found that hypoxia inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) were spatiotemporally co-localized with possible hypoxic regions in embryos. Investigation of platelet endothelial cell adhesion molecule (PECAM) expression provides evidence that endothelial cells proliferate and form the vessels in the hypoxic region in developing organs. Furthermore, we found that hypoxia induced both HIF-1alpha and VEGF in F9 embryonic stem and differentiated cells. Thus, we suggest that hypoxia may exist widely in developing embryonic tissues and that it may act as a signal for embryonic blood vessel formation in vivo.
Lee
Y M
YM
Department of Molecular Biology, Pusan National University, Pusan, Korea.
Jeong
C H
CH
Koo
S Y
SY
Son
M J
MJ
Song
H S
HS
Bae
S K
SK
Raleigh
J A
JA
Chung
H Y
HY
Yoo
M A
MA
Kim
K W
KW
D000818:Animals; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology*; D001921:Brain / Q000166:cytology / Q000196:embryology*; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation; D015687:Cell Hypoxia / Q000502:physiology; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000502:physiology*; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D000860:Hypoxia; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008222:Lymphokines / Q000032:analysis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009593:Nitroimidazoles / Q000032:analysis / Q000276:immunology; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013724:Teratoma; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; C497443:Hif1a protein, mouse; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D009593:Nitroimidazoles; D009687:Nuclear Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C033815:pimonidazole; D003994:Bucladesine