4D atlas of the mouse embryo for precise morphological staging.
After more than a century of research, the mouse remains the gold-standard model system, for it recapitulates human development and disease and is quickly and highly tractable to genetic manipulations. Fundamental to the power and success of using a mouse model is the ability to stage embryonic mouse development accurately. Past staging systems were limited by the technologies of the day, such that only surface features, visible with a light microscope, could be recognized and used to define stages. With the advent of high-throughput 3D imaging tools that capture embryo morphology in microscopic detail, we now present the first 4D atlas staging system for mouse embryonic development using optical projection tomography and image registration methods. By tracking 3D trajectories of every anatomical point in the mouse embryo from E11.5 to E14.0, we established the first 4D atlas compiled from ex vivo 3D mouse embryo reference images. The resulting 4D atlas comprises 51 interpolated 3D images in this gestational range, resulting in a temporal resolution of 72 min. From this 4D atlas, any mouse embryo image can be subsequently compared and staged at the global, voxel and/or structural level. Assigning an embryonic stage to each point in anatomy allows for unprecedented quantitative analysis of developmental asynchrony among different anatomical structures in the same mouse embryo. This comprehensive developmental data set offers developmental biologists a new, powerful staging system that can identify and compare differences in developmental timing in wild-type embryos and shows promise for localizing deviations in mutant development.
Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, M5T 3H7, Canada Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada mwong@mouseimaging.ca.
Michael D
MD
Wong
Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, M5T 3H7, Canada.
Matthijs C
MC
van Eede
Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, M5T 3H7, Canada.
Shoshana
S
Spring
Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, M5T 3H7, Canada.
Stefan
S
Jevtic
Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5E5, Canada.
Julia C
JC
Boughner
Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, M5T 3H7, Canada Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
Jason P
JP
Lerch
Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, M5T 3H7, Canada Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
R Mark
RM
Henkelman
D000818:Animals; D001331:Automation; D004622:Embryo, Mammalian / Q000033:anatomy & histology*; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional / Q000379:methods; D051379:Mice; D010641:Phenotype; D012984:Software; D013997:Time Factors; D041622:Tomography, Optical / Q000379:methods
3D; 4D; Development; Embryo; Imaging; OPT; Staging