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Three-dimensional and molecular analysis of the arterial pole of the developing human heart

Lookup NU author(s): Professor Bob Anderson


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Labeling experiments in chicken and mouse embryos have revealed important roles for different cell lineages in the development of the cardiac arterial pole. These data can only fully be exploited when integrated into the continuously changing morphological context and compared with the patterns of gene expression. As yet, studies on the formation of separate ventricular outlets and arterial trunks in the human heart are exclusively based on histologically stained sections. So as to expand these studies, we performed immunohistochemical analyses of serially sectioned human embryos, along with three-dimensional reconstructions. The development of the cardiac arterial pole involves several parallel and independent processes of formation and fusion of outflow tract cushions, remodeling of the aortic sac and closure of an initial aortopulmonary foramen through formation of a transient aortopulmonary septum. Expression patterns of the transcription factors ISL1, SOX9 and AP2a show that, in addition to fusion of the SOX9-positive endocardial cushions, intrapericardial protrusion of pharyngeal mesenchyme derived from the neural crest contributes to the separation of the developing ascending aorta from the pulmonary trunk. The non-adjacent walls of the intrapericardial arterial trunks are formed through addition of ISL1-positive cells to the distal outflow tract, while the facing parts of the walls form from the protruding mesenchyme. The morphogenetic steps, along with the gene expression patterns reported in this study, are comparable to those observed in the mouse. They confirm the involvement of mesenchymal tissues derived from endocardium, mesoderm and migrating neural crest cells in the process of initial septation of the distal part of the outflow tract, and its subsequent separation into discrete intrapericardial arterial trunks. Key words: aortic arches; heart development; human embryo; outflow tract.

Publication metadata

Author(s): Sizarov A, Lamers WH, Mohun TJ, Brown NA, Anderson RH, Moorman AFM

Publication type: Article

Publication status: Published

Journal: Journal of Anatomy

Year: 2012

Volume: 220

Issue: 4

Pages: 336-349

Print publication date: 01/02/2012

ISSN (print): 0021-8782

ISSN (electronic): 1469-7580

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/j.1469-7580.2012.01474.x


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Funder referenceFunder name
Health-F2-2008-223040European Community
LSHM-CT-2005-018630European Community