Related Experiment Videos
Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND
D Srivastava1, T Thomas, Q Lin
1Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9148, USA. dsriva@mednet.swmed.edu
Insights
dHAND and eHAND transcription factors are crucial for mouse heart development, showing complementary expression in developing ventricles. dHAND gene deletion causes embryonic lethality due to heart failure, revealing its role in right ventricle and aortic arch formation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- dHAND and eHAND are basic helix-loop-helix (bHLH) transcription factors.
- They are expressed in mesodermal and neural crest-derived heart structures.
Purpose of the Study:
- To investigate the expression patterns and functions of dHAND and eHAND during mouse heart development.
- To identify the earliest cardiac chamber-specific transcription factors.
Main Methods:
- Analysis of dHAND and eHAND expression patterns in developing mouse hearts.
- Generation and analysis of dHAND-deficient mouse embryos.
Main Results:
- dHAND and eHAND exhibit complementary expression in the developing mouse heart, restricted to right and left ventricles, respectively.
- dHAND gene deletion leads to embryonic lethality by E10.5 due to heart failure.
- dHAND is essential for the development of the right ventricle and neural crest-derived aortic arches.
Conclusions:
- dHAND and eHAND are the earliest identified cardiac chamber-specific transcription factors.
- dHAND plays a critical role in right ventricular development and aortic arch formation, highlighting a novel cardiogenic subprogram.
Abstract:
dHAND and eHAND are related basic helix-loop-helix (bHLH) transcription factors that are expressed in mesodermal and neural crest-derived structures of the developing heart. In contrast to their homogeneous expression during avian cardiogenesis, during mouse heart development we show that dHAND and eHAND are expressed in a complementary fashion and are restricted to segments of the heart tube fated to form the right and left ventricles, respectively. dHAND and eHAND represent the earliest cardiac chamber-specific transcription factors yet identified. Targeted gene deletion of dHAND in mouse embryos resulted in embryonic lethality at embryonic day 10.5 from heart failure. Our description of the cardiac phenotype of dHAND mutant embryos is the first demonstration of a single gene controlling the formation of the mesodermally derived right ventricle and the neural crest-derived aortic arches and reveals a novel cardiogenic subprogramme for right ventricular development.