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Title: Cardia bifida, defective heart development and abnormal neural crest migration in embryos lacking hypoxia-inducible factor-1alpha
Authors: Compernolle, Veerle ×
Brusselmans, Koenraad
Franco, Diego
Moorman, Antoon
Dewerchin, Mieke
Collen, Desire
Carmeliet, Peter #
Issue Date: Dec-2003
Series Title: Cardiovascular Research vol:60 issue:3 pages:569-79
Abstract: OBJECTIVES: Previous studies have revealed the essential role of hypoxia-inducible factor-1alpha (HIF-1alpha), a basic helix-loop-helix transcription factor, in cardiovascular development. We attempted to further characterize the underlying mechanisms resulting in abnormal cardiogenesis and defective angiogenesis in mice deficient for HIF-1alpha (HIF-1alpha(-/-)). METHODS: We analyzed cardiovascular development in HIF-1alpha(-/-) embryos at both the macroscopic and microscopic level. Gene expression was determined by RT-PCR, in situ hybridization and immunohistochemistry. Embryonic survival was studied using whole embryo culture. RESULTS: HIF-1alpha deficiency caused cardia bifida in some embryos, while cardiac looping was disturbed in others. These defects did not result from abnormal cardiomyocyte commitment or differentiation, but may relate to defective ventricle formation caused by reduced expression of myocyte enhancer factor 2C (MEF2C) and eHAND. In addition, remodeling of the aortic outflow tract and cephalic blood vessels was abnormal in HIF-1alpha(-/-) embryos. These malformations, together with the hypoplastic pharyngeal arches, are presumably induced by defective neural crest cell (NCC) migration. Impaired migration might be related to insufficient levels of semaphorin-3A (Sema3A). Hyperoxia prolonged survival but only partially rescued the developmental program of cultured HIF-1alpha(-/-) embryos. CONCLUSION: HIF-1alpha is essential for proper cardiac development by modulating both neural crest migration and ventricle formation.
ISSN: 0008-6363
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
Clinical and Experimental Endocrinology
Molecular and Vascular Biology
× corresponding author
# (joint) last author

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