Outflow Tract Formation-Embryonic Origins of Conotruncal Congenital Heart Disease.

Sonia Stefanovic,Heather C Etchevers,Stéphane Zaffran

doi:10.3390/jcdd8040042

Sonia Stefanovic, Heather C Etchevers + Show 1 more

Open Access

https://doi.org/10.3390/jcdd8040042

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Abstract

Anomalies in the cardiac outflow tract (OFT) are among the most frequent congenital heart defects (CHDs). During embryogenesis, the cardiac OFT is a dynamic structure at the arterial pole of the heart. Heart tube elongation occurs by addition of cells from pharyngeal, splanchnic mesoderm to both ends. These progenitor cells, termed the second heart field (SHF), were first identified twenty years ago as essential to the growth of the forming heart tube and major contributors to the OFT. Perturbation of SHF development results in common forms of CHDs, including anomalies of the great arteries. OFT development also depends on paracrine interactions between multiple cell types, including myocardial, endocardial and neural crest lineages. In this publication, dedicated to Professor Andriana Gittenberger-De Groot and her contributions to the field of cardiac development and CHDs, we review some of her pioneering studies of OFT development with particular interest in the diverse origins of the many cell types that contribute to the OFT. We also discuss the clinical implications of selected key findings for our understanding of the etiology of CHDs and particularly OFT malformations.

Highlights

Congenital heart defects (CHDs) are the most common form of birth defect, affecting up to 1 in every 100 live births
ASHF progenitors engender the right ventricular and proximal outflow tract (OFT) myocardium, while progenitor cells located in the pSHF contribute to the formation of the atrial and atrioventricular septation through development of the dorsal mesenchymal protrusion (DMP) that forms the muscular base of the primary atrial septum [16]
Integration with transcriptomes of sorted cardiac progenitor cells led to the discovery of novel pSHF markers (Aldh1a2, Bmp4, Gata4, Nr2f2, etc.) that contribute to the formation of the OFT and venous pole of the heart, illustrating how these datasets provide multiple new avenues of investigation for the future [26]

Summary

Introduction

Congenital heart defects (CHDs) are the most common form of birth defect, affecting up to 1 in every 100 live births. ASHF progenitors engender the right ventricular and proximal OFT myocardium, while progenitor cells located in the pSHF contribute to the formation of the atrial and atrioventricular septation through development of the dorsal mesenchymal protrusion (DMP) that forms the muscular base of the primary atrial septum [16]. Cells expressing Cre recombinase under the control of a SHF-restricted regulatory element from the Mef2c transcription factor gene contribute widely to the OFT and right ventricle, as well as to a population of cells at the venous pole of the heart giving rise to the primary atrial septum and the DMP [17,18,19,20]. Integration with transcriptomes of sorted cardiac progenitor cells led to the discovery of novel pSHF markers (Aldh1a2, Bmp, Gata, Nr2f2, etc.) that contribute to the formation of the OFT and venous pole of the heart, illustrating how these datasets provide multiple new avenues of investigation for the future [26]

Endocardial Cushions

Cardiac Neural Crest

RA Signaling Defects Are Associated with DiGeorge Syndrome

Hox Transcription Factors

Other Signaling Pathways

Future Direction and Clinical Implications