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Requirement for AP-2alpha in cardiac outflow tract morphogenesis
Stephanie Brewer1, Xiaobing Jiang, Stephanie Donaldson
1Department of Molecular, Cellular, and Developmental Biology, Yale University, 266 Whitney Avenue, KBT 1034, New Haven, CT 06511, USA.
Mechanisms of Development
|December 18, 2001
Summary
The transcription factor AP-2alpha is crucial for normal heart development. AP-2alpha deficiency in mice leads to outflow tract malformations, indicating its role in cardiac morphogenesis within the neural crest lineage.
Area of Science:
- Developmental Biology
- Genetics
- Cardiovascular Research
Background:
- The transcription factor AP-2alpha is expressed in developing structures.
- Neural crest cells are essential for normal cardiac morphogenesis.
- AP-2alpha expression is prominent in the cardiac neural crest population.
Purpose of the Study:
- To investigate the role of AP-2alpha in cardiac development.
- To determine if AP-2alpha is required for cardiac neural crest migration and outflow tract formation.
Main Methods:
- Generation of a novel AP-2alpha mutant mouse model using homologous recombination with an IRES-lacZ insertion.
- Analysis of cardiac morphology in AP-2alpha-deficient embryos.
- In situ expression analysis of AP-2alpha in cardiac neural crest cells during development.
Main Results:
- AP-2alpha-deficient embryos exhibit significant outflow tract malformations, including double outlet right ventricle and persistent truncus arteriosus.
- AP-2alpha expression is detected in the cardiac neural crest from E9.5-E11.5, coinciding with outflow tract development.
- The distribution of AP-2alpha-expressing cardiac neural crest cells is unaffected in mutant embryos, suggesting AP-2alpha acts within the lineage.
Conclusions:
- AP-2alpha is essential for normal cardiac outflow tract morphogenesis.
- AP-2alpha functions within the neural crest lineage and is not required for cell migration.
- AP-2alpha gene function is necessary before embryonic day 11.5 for proper heart development, potentially mediating interactions between neural crest and surrounding tissues.