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Cardia bifida, defective heart development and abnormal neural crest migration in embryos lacking hypoxia-inducible

Veerle Compernolle1, Koen Brusselmans, Diego Franco

  • 1Flanders Interuniversitary Institute for Biotechnology, KU Leuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.

Cardiovascular Research
|December 9, 2003
PubMed

Insights

Hypoxia-inducible factor-1alpha (HIF-1alpha) is crucial for cardiovascular development. Its deficiency leads to abnormal heart formation and blood vessel development by affecting neural crest cell migration and ventricle formation.

Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Molecular Genetics

Background:

  • Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a vital role in cardiovascular development.
  • Previous studies highlight its importance, but mechanisms of abnormal cardiogenesis and angiogenesis in HIF-1alpha deficient models require further elucidation.

Purpose of the Study:

  • To investigate the mechanisms underlying abnormal cardiogenesis and defective angiogenesis in mice lacking HIF-1alpha (HIF-1alpha(-/-)).

Main Methods:

  • Macroscopic and microscopic analysis of cardiovascular development in HIF-1alpha(-/-) embryos.
  • Gene expression analysis using RT-PCR, in situ hybridization, and immunohistochemistry.
  • Embryonic survival assessment via whole embryo culture under varying oxygen levels.

Main Results:

  • HIF-1alpha deficiency resulted in cardia bifida and disturbed cardiac looping.
  • Defects in ventricle formation were linked to reduced MEF2C and eHAND expression.
  • Abnormal remodeling of aortic outflow tract and cephalic vessels, linked to impaired neural crest cell (NCC) migration and reduced semaphorin-3A (Sema3A) levels.
  • Hyperoxia partially rescued developmental defects in cultured embryos.

Conclusions:

  • HIF-1alpha is essential for normal cardiac development.
  • It regulates cardiac development by influencing neural crest cell migration and ventricle formation.
Abstract

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