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Developmental and genetic aspects of congenital heart disease
1Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9148, USA. dsriva@mednet.swmed.edu
Insights
Researchers identified a gene linked to congenital heart defects (CHDs) by studying transcription factors. This discovery aids in understanding the molecular causes of CHDs and related craniofacial abnormalities.
Area of Science:
- Developmental biology
- Genetics
- Cardiovascular research
Background:
- Congenital heart defects (CHDs) arise from abnormal development of cardiac mesoderm or neural crest.
- The molecular underpinnings of most CHDs are largely unknown.
- Basic helix-loop-helix transcription factors like dHAND and eHAND play roles in heart development.
Purpose of the Study:
- To identify molecular pathways and genes responsible for congenital heart defects.
- To investigate the function of dHAND and eHAND transcription factors in cardiac development.
- To find genes associated with cardiac and craniofacial defects linked to chromosome 22q11 deletion.
Main Methods:
- Studying mouse models lacking the dHAND gene.
- Analyzing gene expression and developmental pathways.
- Searching for dHAND-dependent genes.
Main Results:
- Mice lacking dHAND exhibited hypoplastic right ventricles and abnormal heart vessel development.
- Craniofacial precursor cell death was observed in dHAND-deficient mice.
- A gene potentially responsible for defects in chromosome 22q11 deletion syndrome was identified through dHAND-dependent gene screening.
Conclusions:
- dHAND plays a critical role in right ventricle development and craniofacial formation.
- Identifying dHAND-dependent genes is a viable strategy for discovering CHD-related genes.
- Further systematic dissection of cardiogenesis pathways is crucial for identifying genes causing CHDs.
Abstract:
Congenital heart defects (CHDs) are the result of abnormal cardiac mesoderm or cardiac neural crest development. The molecular cause of most congenital heart disease remains unknown, although numerous cardiac regulatory factors have recently been described. dHAND and eHAND are basic helix-loop-helix transcription factors expressed differentially in the right and left ventricles, respectively, and in the cardiac neural crest. Mice lacking dHAND have a hypoplastic right ventricle and abnormal development of vessels arising from the heart and cell death of craniofacial precursors. By searching for dHAND-dependent genes, a gene likely responsible for the cardiac and craniofacial defects associated with chromosome 22q11 deletion has been identified. A systematic dissection of molecular pathways involved in cardiogenesis should allow for further identification of genes responsible for CHD.