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HAND proteins: molecular mediators of cardiac development and congenital heart disease
1Department of Pediatric Cardiology, University of Texas Southwestern Medical Center, Dallas 75235-9148, USA.
Insights
Basic helix-loop-helix transcription factors dHAND and eHAND regulate embryonic heart development. Mutations in dHAND cause congenital heart defects, revealing pathways in cardiac morphogenesis.
Area of Science:
- Developmental biology
- Cardiovascular research
- Genetics
Background:
- Congenital heart defects (CHDs) arise from embryonic cardiac development anomalies.
- Understanding the molecular basis of CHDs requires a segmental approach to cardiac development.
- Transcription factors play crucial roles in heart morphogenesis.
Purpose of the Study:
- To investigate the role of dHAND and eHAND transcription factors in cardiac development.
- To explore the molecular pathways governing normal and abnormal cardiogenesis.
- To analyze the contribution of these factors to specific heart chamber and vessel development.
Main Methods:
- Utilized targeted gene mutations in mouse models.
- Examined expression patterns of dHAND and eHAND in developing cardiac tissues and associated structures.
- Analyzed phenotypic consequences of dHAND and eHAND mutations on organogenesis.
Main Results:
- dHAND and eHAND exhibit complementary expression in developing ventricles and neural crest derivatives.
- dHAND mutations led to hypoplasia of the right ventricle, branchial arches, and aortic arch arteries.
- These findings highlight distinct roles in the morphogenesis of specific cardiac components.
Conclusions:
- dHAND and eHAND are critical regulators of cardiac development and congenital heart disease.
- Mutations in these transcription factors disrupt normal heart morphogenesis.
- Further dissecting their molecular pathways offers insights into preventing and treating CHDs.
Abstract:
Congenital heart defects are the clinical manifestation of anomalies in embryonic cardiac development. Such defects occur in distinct regions or chambers of the heart. A molecular framework in which to consider cardiac development and congenital heart disease in a segmental fashion has begun to emerge. dHAND and eHAND are two related basic helix-loop-helix transcription factors that are expressed in a complementary fashion in the developing right and left ventricles, respectively. They are also expressed in the neural crest-derived cardiac outflow tract and aortic arch arteries. Targeted mutations of dHAND and eHAND in mice have revealed novel pathways of organogenesis in mesodermal and neural crest derivatives. dHAND mutants exhibit hypoplasia of the right ventricle, branchial arches, and aortic arch arteries. The distinct nature of cardiac defects in dHAND mutants provides an entry into dissecting molecular pathways governing morphogenesis of specific components of the heart. Congenital heart disease is considered as a defect in segmental development of the heart and the role of dHAND and eHAND in regulating such developmental pathways in normal and abnormal cardiogenesis is examined.