The Edinburgh Mouse Atlas: A Digital Atlas of Mouse Development Volume 1 E5.5 to E9.0

The Mouse Atlas Project

This CD is produced as part of the Mouse Atlas Project, a collaboration between the Medical Research Council Human Genetics Unit and the Department of Biomedical Sciences, University of Edinburgh. The aim of the project is to develop a set of digital model mouse embryos.  These will provide a standard reference 'Atlas' complementary to conventional paper atlases. The digital atlas will contain much more detail, but it's major advantages will be the capability to explore the embryo in three dimensions and the almost unlimited possibilities for extension of information content. In addition to providing an atlas of mouse development, the models, and the databases associated with them, have been designed to function as a bioinformatics framework for future projects to map gene-expression patterns and other spatio-temporally organised data. As a background to the use of this CD, we discuss below some of the implications of these aspects of design.  It is worth emphasising, however, that the present CD is offered as a stand-alone Atlas with no gene expression database facility.  The single developmental stage available on the first CD will be complemented by other stages up to 8.5 days development early in 2000 and by later stages of development as they are completed (we are currently working on 12.5 day and 17.5 day models). A prototype database system for in situ gene expression patterns has been developed at the MRC HGU for use with the Atlas. At present this contains only test data and is not yet funded as a public resource.  We plan to make a public graphical gene expression database available by the end of 2001. This will complement the existing text-based gene expression database, the GXD, which is based at the Jackson Laboratory.

The bioinformatics framework of the Mouse Atlas has two basic components; one spatial, the other textual. For the spatial component, the idea is to provide a standard spatial reference frame onto which information, such as gene expression domains, can be mapped. This then will enable query of the database on spatial terms involving relationships such as position, orientation, direction, shape, etc. The design requirements for the spatial reference frame are as follows. It must be possible to map data into the reference frame from sectioned material, whole-mounts and  3-D reconstructions. This mapping should be context-free in the sense that the reference frame should not necessarily be restricted by prior interpretation of the space, for example by requiring delineated anatomical regions. The best option for this purpose is a 3-D digital embryo in the form of a voxel model as shown in figure 1. (A 2-D digitial image is often represented as a 2-D rectangular array of grey or colour values termed pixels, similarly a 3-D image is represented as a 3-D rectangular array of values termed voxels.)  One way to make such a model is by reconstruction from images of tissue sections stained using standard histological preparations (e.g. H&E). The digital model can then be re-sectioned in any plane to allow mapping from section data and can be visualised in 3D for mapping from whole mount. This CD-ROM provides such a 3D digital model of a single embryo, that for the 9-day mouse embryo (Theiler Stage 14).  The CD also contains the set of original digitised images of all 305 sections and software tools for viewing the data.
 
 

Full size

Figure 1: 3D visualisation of the Theiler stage 14 voxel model as a "cut block" also shown are surface rendered views of selected anatomical components. None of the visible surfaces of the block are original digitised sections. The vertical sides are orthogonal planes perpendicular to the original and the top surface is at an arbitrary angle.

The textual component of the Mouse Atlas is a controlled vocabulary for embryo anatomy. This vocabulary has been implemented in the form of a part-of hierarchy and realised as an object-oriented database accessible over the Internet (see the genex anatomy database page).  Primary access to the nomenclature is via a Java user-interface (figure 2) but a simple text-list is also available. This nomenclature is being used for annotating gene-expression patterns in the GXD and will also be used for supplementary annotation within our spatially mapped gene-expression database.
 
 

Full size

Figure 2: A partially expanded view of the Theiler stage 14 anatomical nomenclature. This is a view of part of the Java interface that is provided from the anatomy database pages.

The spatial description is linked to a textual anatomy by mapping the textual terms onto the standard coordinate space. The regions or domains corresponding to the anatomical components have been delineated (using the program MAPaint, and image-processing tools) within the voxel models.

The combination of spatial reference frame, anatomical nomenclature and anatomical mappings, is called the Edinburgh Mouse Atlas (figure 3). For more details on the database please see our Mouse Atlas web pages.
 
 

Full size

Figure 3: The three components of the Edinburgh Mouse Atlas: voxel model of histology, standard anatomical nomenclature linked to anatomical domains in 3D space. All components of this Atlas are on this CD-ROM and are held in an Object Oriented database as a reference framework for a gene-expression database.

The CD

We would be very happy to collaborate with experts in different aspects of developmental anatomy who may wish to help delineate - or advise on the delineation of - individual tissues and organs in any of these models, including the 9-day model.  Full credit will, of course, be given to all collaborators.
 

The CD provides the user with the voxel model and anatomical domains. In later versions of the CD, each Theiler stage reconstruction will appear under its own section so that the data can be accessed either by following the links or by starting up SectionView and reading in the required Theiler stage using the  "File->Theiler stage" menu.

We have provided two ways to view the voxel models and anatomical domains.  First, 'EmbryoView' allows the user to see the embryo as a whole and to rotate it interactively. EmbryoView uses the public domain software VTK to make the images and can be run on any machine with a Java enabled browser (see Getting the Applets Going).   Second, 'SectionView' (a variant of our own software, 'MAPaint') will allow arbitrary re-sectioning of the voxel model with an overlay colour for user-selected anatomy. This programme also allows the user to "click" on any voxel to get the name of the underlying anatomical component. This program is currently only for Unix machines. Users with other operating systems can see the histology images with the Java "Section Chooser" (e.g. Theiler 14 - E9) or the html table (e.g. Theiler 14 - E9).The hierarchical anatomical nomenclature is organised on the CD in a directory structure that matches the anatomy database. This directory structure can be explored using the file manager on your own machine.

Follow the links for more detail on the methods used to develop this atlas and on how the tools can be used to help you analyse your own data.

References

• Baldock, R., Bard, J., Kaufman, M., and Davidson, D. (1992). A real mouse for your computer. Bioessays. 14, 501-502.
• Bard, J.B.L., Kaufman, M.H. Dubreuil, C., Brune, R.M., Burger, A., Baldock, R.A., and Davidson, D. (1998) An internet-accessible database of mouse developmental anatomy based on a systematic nomenclature. Mechanisms of Development, 74, 111-120.
• Brune, R.M., Bard, J.B.L., Dubreuil, C., Guest, E., W. Hill, M. Kaufman, M. Stark, D. Davidson, and R. A.  Baldock. (1999). A Three-Dimensional Model of the Mouse at Embryonic Day 9.  Developmental Biology  216(2),  457-68.
• Davidson, D., Bard, J., Brune, R., Burger, A., Dubreuil, C., Hill, W., Kaufman, M., Quinn, J., Stark, M., and Baldock, R. (1997). The mouse atlas and graphical gene-expression database.  Seminars In Cell & Developmental Biology 8, 509-517.
• Guest, E. and Baldock, R.A. "Automatic Reconstruction of Serial Sections Using the Finite Element Method", Bioimaging 3, 154-167, 1995.
• Kaufman, (1992). The Atlas of Mouse Development, Academic Press, London
• Ringwald, M., Baldock, R., Bard, J., Kaufman, M., Eppig, J.T., Richardson, J.E., Nadeau, J.H., and Davidson, D. (1994). A database for mouse development.  Science 265, 2033-2034.
• Theiler, K. (1989). The House Mouse: Atlas of Embryonic Development. Springer, New York