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Updated: May 23, 2026
A Pipeline to Characterize Structural Heart Defects in the Fetal Mouse
Published on: December 16, 2022
Normal and abnormal development of the intrapericardial arterial trunks in humans and mice
Robert H Anderson1, Bill Chaudhry, Timothy J Mohun
1Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne, UK.
Insights
Researchers clarified the development of cardiac arterial trunks by identifying a transient aortopulmonary foramen closure mechanism. This provides new insights into congenital heart defects like common arterial trunk.
Area of Science:
- Developmental biology
- Cardiovascular research
- Embryology
Background:
- The cardiac outflow tract comprises intrapericardial arterial trunks, arterial roots with valves, and ventricular outflow tracts.
- Understanding the development of the arterial trunks is crucial for identifying congenital heart abnormalities.
Purpose of the Study:
- To investigate the normal and abnormal development of the distal arterial trunks.
- To compare findings in mouse and human embryonic development.
Main Methods:
- Utilized lineage tracing and 3D visualization techniques (episocpic reconstruction, scanning electron microscopy).
- Examined embryonic mouse hearts from day 9.5 to 12.5.
Main Results:
- Characterized a transient aortopulmonary (AP) foramen between the aortic sac protrusion and outflow cushions.
- Demonstrated closure of the AP foramen by fusion of the protrusion (with neural crest cells) and outflow cushions, forming a temporary AP septum.
- Identified the origins of the intrapericardial trunk walls from the protrusion, outflow cushions, and second heart field mesenchyme.
Conclusions:
- Provided objective evidence for the mechanisms of AP foramen closure in developing arterial trunks.
- Offered insights into the formation of aortopulmonary windows and variations of common arterial trunk.
Aims:
The definitive cardiac outflow channels have three components: the intrapericardial arterial trunks; the arterial roots with valves; and the ventricular outflow tracts (OFTs). We studied the normal and abnormal development of the most distal of these, the arterial trunks, comparing findings in mice and humans.
Methods And Results:
Using lineage tracing and three-dimensional visualization by episcopic reconstruction and scanning electron microscopy, we studied embryonic day 9.5-12.5 mouse hearts, clarifying the development of the OFTs distal to the primordia of the arterial valves. We characterize a transient aortopulmonary (AP) foramen, located between the leading edge of a protrusion from the dorsal wall of the aortic sac and the distal margins of the two outflow cushions. The foramen is closed by fusion of the protrusion, with its cap of neural crest cells (NCCs), with the NCC-filled cushions; the resulting structure then functioning transiently as an AP septum. Only subsequent to this closure is it possible to recognize, more proximally, the previously described AP septal complex. The adjacent walls of the intrapericardial trunks are derived from the protrusion and distal parts of the outflow cushions, whereas the lateral walls are formed from intrapericardial extensions of the pharyngeal mesenchyme derived from the second heart field.
Conclusions:
We provide, for the first time, objective evidence of the mechanisms of closure of an AP foramen that exists distally between the lumens of the developing intrapericardial arterial trunks. Our findings provide insights into the formation of AP windows and the variants of common arterial trunk.
