Gene expression profiling of the forming atrioventricular node using a novel tbx3-based node-specific transgenic
Thomas Horsthuis1, Henk P J Buermans, Janynke F Brons
1Heart Failure Research Center, University of Amsterdam, The Netherlands.
Circulation Research
|June 6, 2009
Summary
This study reveals distinct gene programs controlling atrioventricular (AV) node development and function. It identifies novel molecular pathways and shared characteristics with nervous system development, offering insights into cardiac arrhythmias.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Molecular Genetics
Background:
- The atrioventricular (AV) node is crucial for cardiac rhythm but its developmental control and molecular phenotype are poorly understood.
- Limited data exist on the specific gene programs governing AV node formation and function, impacting our understanding of related arrhythmias.
Purpose of the Study:
- To investigate the gene programs controlling the development and molecular phenotype of the AV node using a novel reporter mouse model.
- To identify specific molecular markers and pathways differentiating AV nodal myocardium from working chamber myocardium during embryonic development.
Main Methods:
- Utilized a novel AV nodal myocardium-specific reporter mouse model with green fluorescent protein (GFP) expression driven by Tbx3 regulatory elements.
- Employed fluorescence-activated cell sorting (FACS) to isolate embryonic AV nodal and chamber myocardial cells.
- Performed genome-wide microarray analysis to assess gene expression profiles of purified cell populations.
Main Results:
- Demonstrated selective GFP expression in the AV node, distinct from the AV bundle and sinus node, indicating unique regulatory pathways.
- Generated comprehensive lists of sodium, calcium, and potassium channel genes specific to developing nodal and chamber myocardium.
- Revealed divergence of AV node and chamber myocardium phenotypes during development while maintaining functional gene classes.
- Identified neurotrophic factors and semaphorins in AV node gene profiles, suggesting shared developmental pathways with the nervous system.
Conclusions:
- Distinct regulatory sequences and pathways control gene expression in different components of the cardiac conduction system.
- The study provides valuable molecular insights into AV node development and its divergence from working myocardium.
- Novel roles for neurotrophic factors and semaphorins in AV node development are suggested, highlighting connections to neural development.
