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Published Online October 9, 2008
Science DOI: 10.1126/science.1162493

Research Articles

Submitted on June 30, 2008
Accepted on October 1, 2008

Reconstruction of Zebrafish Early Embryonic Development by Scanned Light Sheet Microscopy

Philipp J. Keller 1*, Annette D. Schmidt 2, Joachim Wittbrodt 3*, Ernst H. K. Stelzer 4

1 Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany; Developmental Biology Unit, EMBL, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
2 Developmental Biology Unit, EMBL, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
3 Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany; Developmental Biology Unit, EMBL, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. ; Institute of Zoology, Department for Developmental Physiology, University of Heidelberg, INF 230, D-69120 Heidelberg, Germany. ; Institute of Toxicology and Genetics, Karlsruhe Institute of Technology (KIT), Post Office Box 3640, D-76021 Karlsruhe, Germany.
4 Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany.

* To whom correspondence should be addressed.
Philipp J. Keller , E-mail: keller{at}embl.de
Joachim Wittbrodt , E-mail: wittbrod{at}embl.de

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" (i.e., 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.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)