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Normal and abnormal development of the intrapericardial arterial trunks in humans and mice

Lookup NU author(s): Professor Bob Anderson, Dr Bill Chaudhry, Dr Simon BamforthORCiD, Dr Darren Hoyland, Dr Helen PhillipsORCiD, Professor Deborah HendersonORCiD

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Abstract

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.


Publication metadata

Author(s): Anderson RH, Chaudhry B, Mohun TJ, Bamforth SD, Hoyland D, Phillips HM, Webb S, Moorman AF, Brown NA, Henderson DJ

Publication type: Article

Publication status: Published

Journal: Cardiovascular Research

Year: 2012

Volume: 95

Issue: 1

Pages: 108-115

Print publication date: 12/04/2012

ISSN (print): 0008-6363

ISSN (electronic): 1755-3245

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/cvr/cvs147

DOI: 10.1093/cvr/cvs147


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Funding

Funder referenceFunder name
018630European Commission
261057European Network for Translational Research in Atrial Fibrillation
RG/03/012British Heart Foundation
RG/07/007British Heart Foundation
U117562103Medical Research Council UK

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