To download an animation of the 3D reconstructed Patch embryo, click here. A Microsoft Windows-compatible animation viewer can be downloaded by clicking here.
Betsey S. Williams, Ph.D. & Michael D. Doyle, Ph.D. Muritech Co.
A project is described to develop a prototype two- and three-dimensional color atlas of mouse development that will provide both academic and industrial biologists with a set of computer tools to assess and analyze experimental data from normal and abnormal mouse embryos. We chose the 13 1/2 day normal mouse embryo and a PATCH mutant of the same age to demonstrate how such a multidimensional atlas, with an integrated knowledge base, will provide researchers the ability to identify anatomical structures at several levels of resolution and to diagnose abnormal development and dysmorphologies. Standard methods of preparation of serial sections are being used in order to mimic the methods most commonly employed in research laboratories. An external registration marker system has been introduced into the paraffin embedding process to allow precise spatial calibration, correction for warping artifacts, and to aid in the three dimensional reconstruction of embryonic anatomy.
Color micrographic images of histological cross sections are digitized at very high resolution and are processed to create color voxel datasets representative of 3-dimensional embryonic morphology. Important anatomical structures are identified and encoded into an anatomical knowledge base using the patented MetaMAP (TM) process. These data, together with a set of associated analytical tools, will be integrated into a multimedia online information resource that will be accessible via the Internet's World Wide Web, using a modified (patent pending) version of the Mosaic program from the National Center for Supercomputer Applications. Users will be able to browse through 3D reconstructions of mouse embryos at various stages, interactively rotate, slice through, and examine fine detail in any of those reconstructions. Important anatomical structures will be instantly identified when the user clicks, with the computer "mouse," on any voxel in the database. Various interactive analytical tools will also be provided to allow scientists to compare their own specimens with the online "standards."
Both online and CDROM versions of the database will be developed. Future endeavors will include: 1) the completion of the two and three dimensional color computer atlas of mouse development with constructions at half day intervals (or greater when necessary) over the total embryonic period; 2) expansion of the atlas to include higher levels of microscopic resolution, and the reconstruction of histochemical and expression data (both at the protein and nucleic acid level); 3) development of computer tools to interactively "paint" expression data, pro duced by research laboratories, onto reconstructed mouse embryonic models; 4) the development of computer generated methods to automatically classify dysmorphologies by comparison to the standard mouse models; 5) the use of magnetic resonance microscopy as an additional imaging method; 6) integration of this datasbase with other databases, such as the Mouse Genome Project at the Jackson Laboratories; and 7) the establishment of a service for the research community that would prepare, digitize, reconstruct and analyze any samples (organs, mutants, etc).
To download an animation of the 3D reconstructed Patch embryo, click here. A Microsoft Windows-compatible animation viewer can be downloaded by clicking here.