Co-Authors:
Yang, J., Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Ludwigstr. 43, Bad Nauheim 61231, Germany, Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
Bücker, S., Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Ludwigstr. 43, Bad Nauheim 61231, Germany
Jungblut, B., Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Ludwigstr. 43, Bad Nauheim 61231, Germany
Böttger, T., Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Ludwigstr. 43, Bad Nauheim 61231, Germany
Cinnamon, Y., Developmental Biology Division, National Institute for Medical Research, Mill Hill, United Kingdom
Tchorz, J., Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Basel, Switzerland, Department of Biomedicine, University of Basel, Institute of Physiology, Basel, Switzerland
Müller, M., Developmental and Molecular Pathways, Novartis Institutes for BioMedical Research, Basel, Switzerland
Bettler, B., Department of Biomedicine, University of Basel, Institute of Physiology, Basel, Switzerland
Harvey, R., Victor Chang Cardiac Research Institute, St Vincent's Hospital, Darlinghurst, Australia
Sun, Q.-Y., Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
Schneider, A., Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Ludwigstr. 43, Bad Nauheim 61231, Germany
Braun, T., Department of Cardiac Development and Remodelling, Max-Planck-Institute for Heart and Lung Research, Ludwigstr. 43, Bad Nauheim 61231, Germany
Abstract:
AimsThe ventricular wall of the heart is composed of trabeculated and compact layers, which are separated by yet unknown processes during embryonic development. Here, we wanted to explore the role of Notch2 and Numb/Numblike for myocardial trabeculation and compaction.Methods and resultsWe found that Notch2 activity is specifically down-regulated in the compact layer during cardiac development in the mouse. The biological role of Notch2 down-regulation was investigated by the expression of constitutively active Notch2 in the myocardium of transgenic mice, resulting in hypertrabeculation, reduced compaction, and ventricular septum defects. To disclose the mechanism that inhibited Notch2 activity during the formation of myocardial layers, we analysed potential suppressors of Notch signalling. We unveiled that concomitant but not separate ablation of Numb and Numblike in the developing heart leads to increased Notch2 activity along with hypertrabeculation, reduced compaction, and ventricular septum defects, phenocopying effects gained by overexpression of constitutively active Notch2. Expression profiling revealed a strong up-regulation of Bmp10 in Numb/Numblike mutant hearts, which might also interfere with trabeculation and compaction.ConclusionThis study identified potential novel roles of Numb/Numblike in regulating trabeculation and compaction by inhibiting Notch2 and Bmp10 signalling. © 2012 The Author.
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