Cell-accurate optical mapping across the entire developing heart.

Michael Weber,Jan Huisken,Peter Kohl,Nico Scherf,Daniela Panáková,Alexander M Meyer

doi:10.7554/elife.28307

Abstract

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.

Highlights

Organogenesis builds on cell–cell interactions that shape tissue properties, and tissue-level cues that control maturation of cell structure and function
Region-specific heterogeneity in cellular activity patterns evolves as the heart undergoes large-scale morphological changes: The spontaneously active heart tube develops into the mature heart, in which pacemaker cells near the inflow site initiate the rhythmic excitation that spreads with differential velocities through distinct regions of the myocardium
By noninvasively reconstructing the maturation process of the myocardium in its entirety at cellular resolution, our approach offers an integrative perspective on tissue and cell levels simultaneously, which has previously required separate experimental setups and

Summary

Introduction

Organogenesis builds on cell–cell interactions that shape tissue properties, and tissue-level cues that control maturation of cell structure and function. Region-specific heterogeneity in cellular activity patterns evolves as the heart undergoes large-scale morphological changes: The spontaneously active heart tube develops into the mature heart, in which pacemaker cells near the inflow site initiate the rhythmic excitation that spreads with differential velocities through distinct regions of the myocardium. This controlled cardiac activation gives rise to an orderly sequence of atrial and ventricular calcium release and contraction. By noninvasively reconstructing the maturation process of the myocardium in its entirety at cellular resolution, our approach offers an integrative perspective on tissue and cell levels simultaneously, which has previously required separate experimental setups and

Methods

Results

Conclusion