keynote: Prof. dr. Antoon F.M. Moorman

Antoon Moorman Professor Emeritus of Embryology
Department of Anatomy, Embryology & Physiology
Academic Medical Center, University of Amsterdam

Development of the cardiac building plan

Molecular and genetic studies around the turn of this century have revolutionized the field of cardiac development. By molecular genetic lineage analyses and detailed quantitative reconstructions of cardiac growth, we now know that the primary heart tube, as seen in the early embryo contains little more than the precursors for the left ventricle, whereas the precursor cells for the remainder of the cardiac components are continuously added, to both the venous and arterial pole of the heart tube, from a single center of growth outside the heart. Therefore, it is impossible that the straight heart tube contains the precursors for the conduction system as rings separating the purported cardiac segments.

While the primary heart tube is growing by addition of cells, it does not show significant cell proliferation, until chamber differentiation and expansion starts locally in the tube, by which the chambers balloon from the primary heart tube. The transcriptional repressors Tbx2 and Tbx3 locally repress the chamber-specific program of gene expression, by which these regions are allowed to differentiate into the distinct components of the conduction system. Detailed reconstructions of the developmental patterns of expression of Tbx3 during development have revealed, that Tbx3 is expressed in those areas of the heart tube that do not become chamber, i.e. in the sinu-nodal region, internodal region, atrioventricular junction, atrioventricular bundle and bundle branches. These areas comprise not only the conventional conduction system, but also the highly controversial areas of the internodal region and the entire atrioventricular junction. Also the (right) ventricular outflow tract initially expresses these transcriptional repressors, preventing it from chamber differentiation. These observations provide an embryonic basis why some areas in the heart are more arrhythmogenic than other regions. Comparative evolutionary developmental studies have shown that the cardiac building plan is conserved from fish to man.

Short biosketch:
Antoon Moorman (1947) did his university studies in biology and chemistry. Subsequent to his PhD, he continued his career in the Department of Anatomy & Embryology, where he became professor of Embryology and head of the Department. His research interest became focused on the development of the heart. Trained as a molecular biologist he soon discovered that meaningful analysis of its development requires an integrated molecular and morphological approach in a quantitative 3-dimensional fashion, which nowadays is considered as a systems biological approach of the heart. His lab has become finesse in producing computer-based 3D-gene expression reconstructions to clarify the intricate three-dimensional development of the cardiac chambers and the conduction system. He coordinated the Dutch Heart Foundation Molecular Cardiology program: “Cardiac Healing & Rejuvenation” (1996-2009), The FP6 EU program: “HeartRepair” (2005-2009) and the FP7 EU program: “CHeartED” (2009-2013). He published more than 400 articles and was knighted in the Order of the Dutch Lion in 2012.
(For an interview see: (Ozkan J, 2012) Pioneer who gave shape to Cardiac Morphology: Antoon FM Moorman, PhD, FESC. Circulation 126 (8), F43-F48)

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