Computer-based three-dimensional visualization of developmental gene expression


A broad understanding of the relationship between gene activation, pattern formation and morphogenesis will require adequate tools for three-dimensional and, perhaps four-dimensional, representation and analysis of molecular developmental processes. We present a novel, computer-based method for the 3D visualization of embryonic gene expression and morphological structures from serial sections. The information from these automatically aligned 3D reconstructions exceeds that from single-section and whole-mount visualizations of in situ hybridizations. In addition, these 3D models of gene-expression patterns can become a central component of a future developmental database designed for the collection and presentation of digitized, morphological and gene-expression data. This work is accompanied by a web site (

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Figure 1: Illustration of the 3D-reconstruction concept.
Figure 2: 3D models of embryonic structures and gene expression patterns, demonstrating reconstructions from three different structural levels.
Figure 3: Precision of the congruencing of sections.
Figure 4: Stereo-images of Myf5 expression in the rostral thorax and forelimb anlagen of a TS18 mouse embryo (148 sections cut at 7 μm; total specimen size, 1.036 mm).
Figure 5: Schematic organization chart for a 3D gene-expression database.


  1. 1

    Ringwald, M. et al. A database for mouse development. Science 265, 2033–2034 (1994).

  2. 2

    Roush, W. A womb with a view. Science 278, 1397–1399 (1997).

  3. 3

    His, W. Ueber die Methoden der plastischen Rekonstruktion und über deren Bedeutung für Anatomie und Entwicklungsgeschichte. Anat. Anz. II, 382–392 (1887).

  4. 4

    Born, G. Die Plattenmodelliermethode. Archiv f. mikroskop. Anatomie 22, 584–599 (1883).

  5. 5

    Sjöstrand, R.F. Ultrastructure of retinal rod synapses of the guinea pig eye as revealed by 3-D reconstructions from serial sections. J. Ultrastruct. Res. 2, 122–170 (1958).

  6. 6

    Arnolds, W.J.A. Oriented embedding of small objects in agar-paraffin, with reference marks for serial section reconstruction. Stain Technol. 53, 287–288 (1978).

  7. 7

    Mitchie, A. & Aggerwal, J.K. Contour registration by shape specific points for shape matching. Comput. Graph. Image Processing 22, 296–308 (1983).

  8. 8

    Prothero, J.S. & Prothero, J.W. Three-dimensional reconstruction from serial sections. IV. The reassembly problem. Comput. Biomed. Res. 19, 361–373 (1986).

  9. 9

    Huijsmans, D.P., Lamers, W.H., Los, J.A. & Strackee, J. Toward computerized morphometric facilities: a review of 58 software packages for computer-aided three-dimensional reconstruction, quantification, and picture generation from parallel serial sections. Anat. Rec. 216, 449–470 (1986).

  10. 10

    Braverman, M.S. & Braverman, I.M. Three-dimensional reconstruction of objects from serial sections using a microcomputer graphics system. J. Invest. Dermatol. 86, 290–294 (1986).

  11. 11

    Hibbard, L.S. & Hawkins, R.A. Objective image alignment for three-dimensional reconstruction of digital autoradiograms. J. Neurosci. Meth. 26, 55–74 (1988).

  12. 12

    Brändle, K. A new method for aligning histological serial sections for three-dimensional reconstruction. Comput. Biomed. Res. 22, 52–62 (1989).

  13. 13

    Moss, V.A., Jenkinson, D., McEwan, P. & Elder, H.Y. Automated image segmentation and serial section reconstruction in microscopy. J. Microsc. 158, 187–196 (1990).

  14. 14

    Keri, C. & Ahnelt, P.K. A low cost computer aided design (CAD) system for 3D-reconstruction from serial sections. J. Neurosci. Methods 37, 241–250 (1991).

  15. 15

    Rydmark, M., Jansson, T., Berthold, C.-H. & Gustavsson, T. Computer-assisted realignment of light micrograph images from consecutive section series of cat cerebral cortex. J. Microsc. 165, 29–47 (1992).

  16. 16

    Arraez Aybar, L.A., Merida Velasco, J.R., Rodriguez Vazquez, J. & Jimenez Collado, J. A computerised technique for morphometry and 3D reconstruction of embryological structures. Surg. Radiol. Anat. 16, 419–422 (1994).

  17. 17

    Verbeek, F.J., Huijsmans, D.P., Baeten, R.J., Schoutsen, N.J. & Lamers, W.H. Design and implementation of a database and program for 3D reconstruction from serial sections: a data-driven approach. Microsc. Res. Tech. 30, 496–512 (1995).

  18. 18

    Skoglund, T.S., Pascher, R. & Berthold, C.H. A method for 3D reconstruction of neuronal processes using semithin serial sections displayed as a cinematographic sequence. J. Neurosci. Methods 61, 105–111 (1995).

  19. 19

    Streicher, J., Weninger, W.J. & Müller, G.B. External marker based automatic congruencing: a new method of 3D-reconstruction from serial sections. Anat. Rec. 248, 583–602 (1997).

  20. 20

    Scarborough, J., Aiton, J.F., McLachlan, J.C., Smart, S.D. & Whiten, S.C. The study of early human embryos using interactive 3-dimensional computer reconstructions. J. Anat. 191, 117–122 (1997).

  21. 21

    Vazquez, M.D. et al. 3D reconstruction of the mouse's mesonephros. Anat. Histol. Embryol. 27, 283–287 (1998).

  22. 22

    Smith, B.R. Visualizing human embryos. Sci. Am. 280, 76–81 (1999).

  23. 23

    Candia, A.L. et al. Mox-1 and Mox-2 define a novel homeobox subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. Development 116, 1123–1136 (1992).

  24. 24

    Theiler, K. The House Mouse 1–168 (Springer, Berlin, 1972).

  25. 25

    Ott, M.O., Bober, E., Lyons, G., Arnold, H. & Buckingham, M. Early expression of the myogenic regulatory gene, myf-5, in precursor cells of skeletal muscle in the mouse embryo. Development 111, 1097–1107 (1991).

  26. 26

    Anderson, D.J. & Axel, R. Molecular probes for the development and plasticity of neural crest derivatives. Cell 42, 649–662 (1985).

  27. 27

    Stein, R., Mori, N., Matthews, K., Lo, L.C. & Anderson, D.J. The NGF-inducible SCG10 mRNA encodes a novel membrane-bound protein present in growth cones and abundant in developing neurons. Neuron 1, 463–476 (1988).

  28. 28

    Wright, D.E., White, F.A., Gerfen, R.W., Silos Santiago, I. & Snider, W.D. The guidance molecule semaphorin III is expressed in regions of spinal cord and periphery avoided by growing sensory axons. J. Comp. Neurol. 361, 321–333 (1995).

  29. 29

    Tajbakhsh, S. & Spörle, R. Somite development: constructing the vertebrate body. Cell 92, 9–16 (1998).

  30. 30

    Sporle, R., Gunther, T., Struwe, M. & Schughart, K. Severe defects in the formation of epaxial musculature in open brain (opb) mutant mouse embryos. Development 122, 79–86 (1996).

  31. 31

    Hosono, M. et al. Three-dimensional display of cardiac structures using reconstructed magnetic resonance imaging. J. Digit. Imaging 8, 105–115 (1995).

  32. 32

    Iwamoto, Y., Oda, Y., Tsumura, H., Doi, T. & Sugioka, Y. Three-dimensional MRI reconstructions of musculoskeletal tumors. A preliminary evaluation of 2 cases. Acta Orthop. Scand. 66, 80–83 (1995).

  33. 33

    Krams, R. et al. Evaluation of endothelial shear stress and 3D geometry as factors determining the development of atherosclerosis and remodeling in human coronary arteries in vivo. Combining 3D reconstruction from angiography and IVUS (ANGUS) with computational fluid dynamics. Arterioscler. Thromb. Vasc. Biol. 17, 2061–2065 (1997).

  34. 34

    Seidler, H. et al. A comparative study of stereolithographically modelled skulls of Petralona and Broken Hill: implications for future studies of middle Pleistocene hominid evolution. J. Hum. Evol. 33, 691–703 (1997).

  35. 35

    Stevens, J.K., Mills, L.R. & Trogadis, J.E. Three-Dimensional Confocal Microscopy: Volume Investigation Of Biological Specimens (Academic, San Diego, 1994).

  36. 36

    Müller, G.B. & Wagner, G.P. Homology, Hox genes, and developmental integration. Am. Zool. 36, 4–13 (1996).

  37. 37

    Holland, L.Z., Holland, P.W. & Holland, N.D. Revealing homologies between body parts of distantly related animals by in situ hybridization to developmental genes: Amphioxus versus vertebrates. in Molecular Zoology (eds Ferraris, J.D. & Palumbi, S.R.) 267–295 (Wiley-Liss, New York, 1996).

  38. 38

    Sporle, R. & Schughart, K. Paradox segmentation along inter- and intrasomitic borderlines is followed by dysmorphology of the axial skeleton in the open brain (opb) mouse mutant. Dev. Genet. 22, 359–373 (1998).

  39. 39

    Knox, C.K. & Wenstrom, J.C. 3D visualization of neural structures. Proc. Eastern Multiconference Soc. Computer Simulation 12–17 (1990).

  40. 40

    Sporle, R. & Schughart, K. System to identify individual somites and their derivatives in the developing mouse embryo. Dev. Dyn. 210, 216–266 (1997).

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Correspondence to Johannes Streicher.

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