Determination of hypoxic region by hypoxia marker in developing mouse embryos in vivo: A possible signal for vessel development

You Mie Lee, Chul Ho Jeong, Sun Young Koo, Myung Jin Son, Hyun Seok Song, Soo Kyung Bae, James A. Raleigh, Hae Young Chung, Mi Ae Yoo, Kyu Won Kim

Research output: Contribution to journalArticlepeer-review

258 Scopus citations

Abstract

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 immuno-reactivity 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-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were spatiotemporally colocalized 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-1α 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.

Original languageEnglish
Pages (from-to)175-186
Number of pages12
JournalDevelopmental Dynamics
Volume220
Issue number2
DOIs
StatePublished - 2001

Keywords

  • Angiogenesis
  • Embryo
  • HIF-1α
  • Hypoxia
  • PECAM-1
  • Pimonidazole
  • VEGF

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