Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Harvard Medical School, Boston, United States
Nico Scherf
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
Alexander M Meyer
Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany
Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany
Peter Kohl
Institute for Experimental Cardiovascular Medicine, University Heart Centre Freiburg - Bad Krozingen, Faculty of Medicine, Albert-Ludwigs University, Freiburg, Germany
Organogenesis depends on orchestrated interactions between individual cells and morphogenetically relevant cues at the tissue level. This is true for the heart, whose function critically relies on well-ordered communication between neighboring cells, which is established and fine-tuned during embryonic development. For an integrated understanding of the development of structure and function, we need to move from isolated snap-shot observations of either microscopic or macroscopic parameters to simultaneous and, ideally continuous, cell-to-organ scale imaging. We introduce cell-accurate three-dimensional Ca2+-mapping of all cells in the entire electro-mechanically uncoupled heart during the looping stage of live embryonic zebrafish, using high-speed light sheet microscopy and tailored image processing and analysis. We show how myocardial region-specific heterogeneity in cell function emerges during early development and how structural patterning goes hand-in-hand with functional maturation of the entire heart. Our method opens the way to systematic, scale-bridging, in vivo studies of vertebrate organogenesis by cell-accurate structure-function mapping across entire organs.
