Open AccessThe transcription factor EPAS-1/hypoxia-inducible factor 2α plays an important role in vascular remodeling
Author(s) -
Jinliang Peng,
Liyong Zhang,
Linsay Drysdale,
GuoHua Fong
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.140087397
Subject(s) - vasculogenesis , yolk sac , transcription factor , biology , embryonic stem cell , microbiology and biotechnology , hypoxia inducible factors , angiogenesis , embryo , embryogenesis , vascular endothelial growth factor , anatomy , stem cell , gene , genetics , cancer research , progenitor cell , vegf receptors
We have studied the role of the basic helix–loop–helix–PAS transcription factor EPAS-1/hypoxia-inducible factor 2α in vascular development by gene targeting. In ICR/129 Sv outbred background, more than half of the mutants displayed varying degrees of vascular disorganization, typically in the yolk sac, and diedin utero between embryonic day (E)9.5 and E13.5. In mutant embryos directly derived fromEPAS-1 −/− embryonic stem cells (hence in 129 Sv background), all embryos developed severe vascular defects both in the yolk sac and embryo proper and died between E9.5 and E12.5. Normal blood vessels were formed by vasculogenesis but they either fused improperly or failed to assemble into larger vessels later during development. Our results suggest that EPAS-1 plays an important role at postvasculogenesis stages and is required for the remodeling of the primary vascular network into a mature hierarchy pattern.