In toto imaging and reconstruction of post-implantation mouse development at the single-cell level
Open accessAbstract
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Classical imaging technologies (including live-cell), newer structural imaging technologies (such as cryoelectron tomography and soft X-ray tomography), and novel spatial omics technologies offer opportunities to model biomolecules and functions across scales.
“Here, classical imaging technologies,65,100,101 including live-cell, and newer structural imaging technologies, such as cryoelectron tomography and soft X-ray tomography,66,102,103 as well as novel spatial omics technologies,104,105 offer opportunities to model biomolecules and functions across scales.”
From How to build the virtual cell with artificial intelligence: Priorities and opportunities (2024) · cites this paper as [65]
Cites
Adam: A Method for Stochastic Optimization
Kingma, D. P., & Ba, J. (2014) · arXiv · doi:10.48550/arxiv.1412.6980 · Cited by 98,946 · see citing works
Batch Normalization: Accelerating Deep Network Training by Reducing Internal Covariate Shift
Ioffe, S., & Szegedy, C. (2015) · arXiv · doi:10.48550/arxiv.1502.03167 · Cited by 27,818 · see citing works
A method for registration of 3-D shapes
Besl, P. J., & McKay, N. D. (1992) · IEEE Transactions on Pattern Analysis and Machine Intelligence · doi:10.1109/34.121791 · Cited by 18,363 · see citing works
The Hungarian method for the assignment problem
Kuhn, H. W. (1955) · Naval Research Logistics Quarterly · doi:10.1002/nav.3800020109 · Cited by 13,120 · see citing works
TensorFlow: Large-Scale Machine Learning on Heterogeneous Distributed Systems
Abadi, M., Agarwal, A., Barham, P., Brevdo, E., Chen, Z., Citro, C., Corrado, G. S., Davis, A., Dean, J., Devin, M., et al. (2016) · arXiv · doi:10.48550/arxiv.1603.04467 · Cited by 9,408 · see citing works
Optical Sectioning Deep Inside Live Embryos by Selective Plane Illumination Microscopy
Huisken, J., Swoger, J., Bene, F. D., Wittbrodt, J., & Stelzer, E. H. K. (2004) · Science · doi:10.1126/science.1100035 · Cited by 2,370 · see citing works
Animating rotation with quaternion curves
Shoemake, K. (1985) · ACM SIGGRAPH Computer Graphics · doi:10.1145/325165.325242 · Cited by 1,735 · see citing works
Reconstruction of Zebrafish Early Embryonic Development by Scanned Light Sheet Microscopy
Keller, P., Schmidt, A. D., Wittbrodt, J., & Stelzer, E. H. K. (2008) · Science · doi:10.1126/science.1162493 · Cited by 1,569 · see citing works
Self-citationA New Statistical Approach to Geographic Variation Analysis
Gabriel, K. R., & Sokal, R. R. (1969) · Systematic Zoology · doi:10.2307/2412323 · Cited by 1,289 · see citing works
Astola, J. T., Haavisto, P., & Neuvo, Y. A. (1990) · Proceedings of the IEEE · doi:10.1109/5.54807 · Cited by 1,141 · see citing works
Primordial germ cells in the mouse embryo during gastrulation
Ginsburg, M., Snow, M. H. L., & McLaren, A. (1990) · Development · doi:10.1242/dev.110.2.521 · Cited by 1,016 · see citing works
Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging
Susaki, E. A., Tainaka, K., Perrin, D., Yukinaga, H., Kuno, A., & Ueda, H. R. (2015) · Nature Protocols · doi:10.1038/nprot.2015.085 · Cited by 821 · see citing works
JAABA: Interactive machine learning for automatic annotation of animal behavior
Kabra, M., Robie, A. A., Rivera-Alba, M., Branson, S., & Branson, K. (2013) · Nature Methods · doi:10.1038/nmeth.2281 · Cited by 644 · see citing works
Self-citationTomer, R., Khairy, K. A., Amat, F., & Keller, P. (2012) · Nature Methods · doi:10.1038/nmeth.2062 · Cited by 538 · see citing works
Self-citationAverage Brain Models: A Convergence Study
Guimond, A., Meunier, J., & Thirion, J. (2000) · Computer Vision and Image Understanding · doi:10.1006/cviu.1999.0815 · Cited by 431 · see citing works
Primordial Germ Cells in MicePreprint
Saitou, M., & Yamaji, M. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008375 · Cited by 418 · see citing works
Matula, D. W., & Sokal, R. R. (1980) · Geographical Analysis · doi:10.1111/j.1538-4632.1980.tb00031.x · Cited by 369 · see citing works
Time-Lapse Analysis of Living Mouse Germ Cell Migration
Molyneaux, K. A., Stallock, J., Schaible, K., & Wylie, C. C. (2001) · Developmental Biology · doi:10.1006/dbio.2001.0436 · Cited by 336 · see citing works
Gu, B., Pósfai, E., & Rossant, J. (2018) · Nature Biotechnology · doi:10.1038/nbt.4166 · Cited by 324 · see citing works
The onset of germ cell migration in the mouse embryo
Anderson, R., Copeland, T. K., Schöler, H. R., et al. (2000) · Mechanisms of Development · doi:10.1016/s0925-4773(99)00271-3 · Cited by 315 · see citing works
Fast, accurate reconstruction of cell lineages from large-scale fluorescence microscopy data
Amat, F., Lemon, W. C., Mossing, D. P., McDole, K., Wan, Y., Branson, K. M., Myers, E. W., & Keller, P. (2014) · Nature Methods · doi:10.1038/nmeth.3036 · Cited by 293 · see citing works
Self-citationBlock Matching: A General Framework to Improve Robustness of Rigid Registration of Medical Images
Sebastien Ourselin, A., Roche, A., Prima, S., & Ayache, N. (2000) · Lecture notes in computer science · doi:10.1007/978-3-540-40899-4_57 · Cited by 285 · see citing works
Lawson, K. A., Pedersen, R. A., & van de Geer, S. (1987) · Development · doi:10.1242/dev.101.3.627 · Cited by 278 · see citing works
Adaptive light-sheet microscopy for long-term, high-resolution imaging in living organisms
Royer, L. A., Lemon, W. C., Chhetri, R. K., Wan, Y., Coleman, M., Myers, E. W., & Keller, P. (2016) · Nature Biotechnology · doi:10.1038/nbt.3708 · Cited by 277 · see citing works
Self-citationTam, P., Parameswaran, M., Kinder, S. J., & Weinberger, R. P. (1997) · Development · doi:10.1242/dev.124.9.1631 · Cited by 274 · see citing works
Establishment of conditional reporter mouse lines at ROSA26 locus for live cell imaging
Abe, T., Kiyonari, H., Shioi, G., Inoue, K., Nakao, K., Aizawa, S., & Fujimori, T. (2011) · genesis · doi:10.1002/dvg.20753 · Cited by 251 · see citing works
Whole-animal functional and developmental imaging with isotropic spatial resolution
Chhetri, R. K., Amat, F., Wan, Y., Höckendorf, B., Lemon, W. C., & Keller, P. (2015) · Nature Methods · doi:10.1038/nmeth.3632 · Cited by 237 · see citing works
Self-citationUse of the viral 2A peptide for bicistronic expression in transgenic mice
Trichas, G., Begbie, J., & Srinivas, S. (2008) · BMC Biology · doi:10.1186/1741-7007-6-40 · Cited by 236 · see citing works
Inverted light-sheet microscope for imaging mouse pre-implantation development
Strnad, P., Günther, S., Reichmann, J., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3690 · Cited by 207 · see citing works
Wolff, C., Tinévez, J.-Y., Pietzsch, T., Stamataki, E., Harich, B., Guignard, L., Preibisch, S., Shorte, S. L., Keller, P., Tomančák, P., et al. (2018) · eLife · doi:10.7554/elife.34410 · Cited by 178 · see citing works
Self-citationClonal Analysis of Cell Fate During Gastrulation and Early Neurulation in the Mouse
Lawson, K. A., & Pedersen, R. A. (2007) · Novartis Foundation symposium · doi:10.1002/9780470514221.ch2 · Cited by 177 · see citing works
Establishment and Organization of Germ Layers in the Gastrulating Mouse Embryo
Tam, P., & Beddington, R. S. P. (2007) · Novartis Foundation symposium · doi:10.1002/9780470514221.ch3 · Cited by 150 · see citing works
The Dynamics of Morphogenesis in the Early Mouse EmbryoPreprint
Rivera‐Pérez, J. A., & Hadjantonakis, A. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a015867 · Cited by 132 · see citing works
Essential Role of Sox2 for the Establishment and Maintenance of the Germ Cell Line
Campolo, F., Gori, M., Favaro, R., Nicolis, S., Pellegrini, M., Botti, F., Rossi, P., Jannini, E., & Dolci, S. (2013) · Stem Cells · doi:10.1002/stem.1392 · Cited by 132 · see citing works
Efficient processing and analysis of large-scale light-sheet microscopy data
Amat, F., Höckendorf, B., Wan, Y., et al. (2015) · Nature Protocols · doi:10.1038/nprot.2015.111 · Cited by 131 · see citing works
Self-citationTakaoka, K., Yamamoto, M., & Hamada, H. (2011) · Nature Cell Biology · doi:10.1038/ncb2251 · Cited by 127 · see citing works
Automated Mitosis Detection of Stem Cell Populations in Phase-Contrast Microscopy Images
Huh, S., Ker, D. F. E., Bise, R., et al. (2010) · IEEE Transactions on Medical Imaging · doi:10.1109/tmi.2010.2089384 · Cited by 126 · see citing works
Dynamic in vivo imaging of postimplantation mammalian embryos using whole embryo culture
Jones, E. A. V., Crotty, D. A., Kulesa, P. M., et al. (2002) · genesis · doi:10.1002/gene.10162 · Cited by 123 · see citing works
Noise reduction by vector median filtering
Liu, Y. (2013) · Geophysics · doi:10.1190/geo2012-0232.1 · Cited by 100 · see citing works
Quantitative imaging of cell dynamics in mouse embryos using light-sheet microscopy
Udan, R. S., Piazza, V. G., Hsu, C., Hadjantonakis, A., & Dickinson, M. E. (2014) · Development · doi:10.1242/dev.111021 · Cited by 98 · see citing works
Charting Brachyury-mediated developmental pathways during early mouse embryogenesis
Lolas, M., Valenzuela, P., Tjian, R., & Liu, Z. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402612111 · Cited by 91 · see citing works
Calretinin neurons in human medial prefrontal cortex (areas 24a,b,c, 32?, and 25)
Gabbott, P. L. A., Jays, P. R. L., & Bacon, S. J. (1997) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19970519)381:4 · Cited by 81 · see citing works
Lawson, K. A. (1999) · The International Journal of Developmental Biology · doi:10.1387/ijdb.10668985 · Cited by 66 · see citing works
Automated pipeline for anatomical phenotyping of mouse embryos using micro-CT
Wong, M. D., Maezawa, Y., Lerch, J. P., & Henkelman, R. M. (2014) · Development · doi:10.1242/dev.107722 · Cited by 62 · see citing works
Ichikawa, T., Nakazato, K., Keller, P., Kajiura‐Kobayashi, H., Stelzer, E. H. K., Mochizuki, A., & Nonaka, S. (2014) · Nature Protocols · doi:10.1038/nprot.2014.035 · Cited by 43 · see citing works
Self-citationImuta, Y., Kiyonari, H., Jang, C., et al. (2013) · genesis · doi:10.1002/dvg.22376 · Cited by 38 · see citing works
Ex Utero Culture and Live Imaging of Mouse Embryos
Piliszek, A., Kwon, G. S., & Hadjantonakis, A. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-210-6_9 · Cited by 35 · see citing works
Traffic jam in the primitive streak: The role of defective mesoderm migration in birth defects
Herion, N. J., Salbaum, J. M., & Kappen, C. (2014) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.23283 · Cited by 30 · see citing works
Complexity of the Delaunay Triangulation of Points on Polyhedral Surfaces
Attali, D., & Boissonnat, J. (2003) · Discrete & Computational Geometry · doi:10.1007/s00454-003-2824-x · Cited by 21 · see citing works
SPATIO-TEMPORAL REGISTRATION OF EMBRYO IMAGES
Godin, C., Fiúza, U.-M., Hufnagel, L., Malandain, L. G., Godin, C., Fiúza, U.-M., Lemaire, P., Al, E., Hal, H. I., Guignard, L., et al. (2013) · Cited by 12 · see citing works
Self-citation3D Haar-like elliptical features for object classification in microscopy
Amat, F., & Keller, P. (2013) · IEEE International Symposium on Biomedical Imaging (ISBI) · doi:10.1109/isbi.2013.6556694 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Deep learning for cellular image analysis
Moen, E., Bannon, D., Kudo, T., Graf, W., Covert, M., & Van Valen, D. (2019) · Nature Methods · doi:10.1038/s41592-019-0403-1 · Cited by 1,225 · see citing works
How to build the virtual cell with artificial intelligence: Priorities and opportunities
Bunne, C., Roohani, Y., Rosen, Y., Gupta, A., Zhang, X., Roed, M., Alexandrov, T., AlQuraishi, M., Brennan, P., Burkhardt, D. B., et al. (2024) · Cell · doi:10.1016/j.cell.2024.11.015 · Cited by 393 · see citing works
“Here, classical imaging technologies, 65,100,101 including live-cell, and newer structural imaging technologies, such as cryoelectron tomography and soft X-ray tomography, 66,102,103 as well as novel spatial omics technologies, 104,105 offer opportunities to model biomolecules and functions across…”
Exploring single cells in space and time during tissue development, homeostasis and regeneration
Mayr, U., Serra, D., & Liberali, P. (2019) · Development · doi:10.1242/dev.176727 · Cited by 63 · see citing works
Peng, G., Cui, G., Ke, J., & Jing, N. (2020) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-120219-083220 · Cited by 42 · see citing works
- Authors
- McDole, K., Guignard, L., Amat, F., Berger, A., Malandain, G., Royer, L. A., Turaga, S. C., Branson, K., & Keller, P. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- McDole, Katie
- Guignard, Léo
- Keller, Philipp J.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 175
- Issue
- 3
- Pages
- 859-876.e33
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2896103138
- Cited by
- 522
- References
- 51
- Citations by year
- 2026: 55 · 2025: 72 · 2024: 67 · 2023: 48 · 2022: 61 · 2021: 77 · 2020: 77 · 2019: 51 · 2018: 13
- FWCI
- 28.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- French National Research Agency (ANR-14-CE11-0013)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- light-sheet microscopy, cell tracking, tissue morphogenesis, gastrulation, organogenesis, developmental atlas, live embryo imaging
- MeSH terms
- Animals, Mice, Inbred C57BL, Models, Statistical, Cell Lineage, Organogenesis, Mice, Gastrulation, Single-Cell Analysis, Optical Imaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review