RESEARCHARTICLE Reconstruction of Zebrafish Early Embryonic Development by Scanned Light Sheet Microscopy

A long-standing goal of biology is to map the behavior of all cells during vertebrate embryogenesis. We developed digital scanned laser light sheet fluorescence microscopy and recorded nuclei localization and movement in entire wild-type and mutant zebrafish embryos over the first 24 hours of development. Multiview in vivo imaging at 1.5 billion voxels per minute provides “digital embryos, ” that is, comprehensive databases of cell positions, divisions, and migratory tracks. Our analysis of global cell division patterns reveals a maternally defined initial morphodynamic symmetry break, which identifies the embryonic body axis. We further derive a model of germ layer formation and show that the mesendoderm forms from one-third of the embryo's cells in a single event. Our digital embryos, with 55 million nucleus entries, are provided as a resource. Model systems such as Caenorhabditiselegans and Ciona intestinalis lendthemselveswell to comprehensive analy-ses at the cellular level, for example, by con-ventional microscopy (1, 2). However, global studies of complex vertebrate species encoun-ter technical limitations. Whereas the forma