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Cell. 2018 Oct 18;175(3):859-876.e33. doi: 10.1016/j.cell.2018.09.031. Epub 2018 Oct 11.

In Toto Imaging and Reconstruction of Post-Implantation Mouse Development at the Single-Cell Level.

Author information

1
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: mcdolek@janelia.hhmi.org.
2
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: guignardl@janelia.hhmi.org.
3
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
4
Université Côte d'Azur, Inria, CNRS, I3S, 06900 Sophia Antipolis, France.
5
Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
6
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: kellerp@janelia.hhmi.org.

Abstract

The mouse embryo has long been central to the study of mammalian development; however, elucidating the cell behaviors governing gastrulation and the formation of tissues and organs remains a fundamental challenge. A major obstacle is the lack of live imaging and image analysis technologies capable of systematically following cellular dynamics across the developing embryo. We developed a light-sheet microscope that adapts itself to the dramatic changes in size, shape, and optical properties of the post-implantation mouse embryo and captures its development from gastrulation to early organogenesis at the cellular level. We furthermore developed a computational framework for reconstructing long-term cell tracks, cell divisions, dynamic fate maps, and maps of tissue morphogenesis across the entire embryo. By jointly analyzing cellular dynamics in multiple embryos registered in space and time, we built a dynamic atlas of post-implantation mouse development that, together with our microscopy and computational methods, is provided as a resource. VIDEO ABSTRACT.

KEYWORDS:

adaptive imaging; cell tracking; computational image analysis; developmental atlas; embryonic development; fate mapping; gastrulation; light-sheet microscopy; mouse; organogenesis

PMID:
30318151
DOI:
10.1016/j.cell.2018.09.031

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