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Twist factor regulation of non-cardiomyocyte cell lineages in the developing heart
Nathan J VanDusen1, Anthony B Firulli
1Riley Heart Research Center, Wells Center for Pediatric Research, Division of Pediatric Cardiology, Department of Medical and Molecular Genetics, Indiana Medical School, 1044 W. Walnut St., Indianapolis, IN 46202-5225, USA.
Insights
Twist-family transcription factors are crucial for heart development in non-cardiomyocyte lineages like the endocardium and epicardium. Understanding their roles is key to treating congenital heart defects and adult cardiac diseases.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Molecular Genetics
Background:
- The heart comprises diverse cell types essential for proper cardiac morphogenesis.
- Twist-family basic helix-loop-helix (bHLH) transcription factors regulate distinct cardiac and extra-cardiac lineages during cardiogenesis.
- Non-cardiomyocyte contributions to heart development and disease are increasingly recognized.
Purpose of the Study:
- To review the function of Twist-family bHLH proteins in extra-cardiac cell populations and the endocardium.
- To focus on regulatory mechanisms, downstream targets, and expression profiles of these factors.
- To highlight the importance of understanding these pathways for congenital and adult cardiac pathologies.
Main Methods:
- Literature review of studies on Twist-family bHLH transcription factors.
- Analysis of regulatory mechanisms, downstream targets, and expression patterns.
- Synthesis of current knowledge on their roles in cardiac development and disease.
Main Results:
- Twist-family bHLH factors exhibit distinct roles in cardiac neural crest (cNCC), epicardium, and endocardium.
- These factors regulate key molecular pathways influencing cardiac development.
- Dysfunction of these factors is linked to congenital heart diseases and adult pathologies like fibrosis.
Conclusions:
- Elucidating Twist-family bHLH functions in non-cardiomyocytes is critical for understanding congenital heart disease.
- Knowledge of these pathways is essential for developing improved treatments for adult cardiac conditions such as myocardial infarction and fibrosis.
- This review provides a foundation for future research into Twist-family bHLH-mediated cardiac pathologies.
Abstract:
The heart is a complex organ that is composed of numerous cell types, which must integrate their programs for proper specification, differentiation and cardiac morphogenesis. During cardiogenesis members of the Twist-family of basic helix-loop-helix (bHLH) transcription factors play distinct roles within cardiac lineages such as the endocardium and extra-cardiac lineages such as the cardiac neural crest (cNCC) and epicardium. While the study of these cell populations is often eclipsed by that of cardiomyocytes, the contributions of non-cardiomyocytes to development and disease are increasingly being appreciated as both dynamic and essential. This review summarizes what is known regarding Twist-family bHLH function in extra-cardiac cell populations and the endocardium, with a focus on regulatory mechanisms, downstream targets, and expression profiles. Improving our understanding of the molecular pathways that Twist-family bHLH factors mediate in these lineages will be necessary to ascertain how their dysfunction leads to congenital disease and adult pathologies such as myocardial infarctions and cardiac fibroblast induced fibrosis. Indeed, this knowledge will prove to be critical to clinicians seeking to improve current treatments.
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