ECB-ART-43198J Chem Biol 2013 Sep 13;71:17-28. doi: 10.1007/s12154-013-0101-x.
Show Gene links Show Anatomy links
Towards 3D in silico modeling of the sea urchin embryonic development.
Embryogenesis is a dynamic process with an intrinsic variability whose understanding requires the integration of molecular, genetic, and cellular dynamics. Biological circuits function over time at the level of single cells and require a precise analysis of the topology, temporality, and probability of events. Integrative developmental biology is currently looking for the appropriate strategies to capture the intrinsic properties of biological systems. The "-omic" approaches require disruption of the function of the biological circuit; they provide static information, with low temporal resolution and usually with population averaging that masks fast or variable features at the cellular scale and in a single individual. This data should be correlated with cell behavior as cells are the integrators of biological activity. Cellular dynamics are captured by the in vivo microscopy observation of live organisms. This can be used to reconstruct the 3D + time cell lineage tree to serve as the basis for modeling the organism''s multiscale dynamics. We discuss here the progress that has been made in this direction, starting with the reconstruction over time of three-dimensional digital embryos from in toto time-lapse imaging. Digital specimens provide the means for a quantitative description of the development of model organisms that can be stored, shared, and compared. They open the way to in silico experimentation and to a more theoretical approach to biological processes. We show, with some unpublished results, how the proposed methodology can be applied to sea urchin species that have been model organisms in the field of classical embryology and modern developmental biology for over a century.
PubMed ID: 24386014
PMC ID: PMC3877407
Article link: J Chem Biol
Genes referenced: LOC100887844 LOC100893907 LOC115919910 LOC115925415 LOC583082
Article Images: [+] show captions
|Fig. 1. From in vivo and in toto observations to in silico experimentation, through the construction of digital embryos and the integration of quantitative data across spatio-temporal scales. From left to right. First column (light blue), volume rendering of experimental raw data displayed as snapshots taken from time-lapse sequences during Paracentrotus lividus embryo development. Second column (blue), surface rendering of digital embryos reconstructed from the raw data shown in the first column. Along the spatial scale, the microscopic level of the reconstructed data is at the single-cell scale (a single cell shown in yellow). The mesoscopic level corresponds to patterns/tissues (e.g., the Veg1 population in pink) and the macroscopic scale to the whole embryo (shown in purple). Third column (pink), quantitative description over time at the micro-, meso- and macroscopic levels extracted from digital embryos. Fourth column (green), theoretical modeling based on biological hypotheses and intended to predict the system behavior is compared with the quantitative observations. The cell is the integrator of subcellular activities including gene regulatory networks (GRNs), cell signaling and morphogen activity|
|Fig. 2. Paracentrotus lividus embryo reconstruction at the 370-cell stage. Raw and reconstructed data displayed with the Mov-It interactive visualization software. Raw data with cell membranes (a) and nuclei (b) staining represented in volume rendering according to the color map displayed bottom right. Colored dots indicate the approximate nucleus center for each cell. Orthoslice in the x y plane for raw membranes (c) and nuclei (d), colored dots as in a,b; in the inset, orthoslices of raw data and their position in the volume indicated by blue lines. e Same as in c, with a cut of the segmented surfaces in addition. f Isosurfaces of segmented membranes. The different cell populations (i.e., small and large micromeres, Veg2 and Veg1 macromeres, and mesomeres) are displayed in different colors, color map described on the right. a–f Referential displayed bottom left. Scale bar 20 μm (Images from Duloquin, L., and Rizzi B., unpublished)|
|Fig. 3. Cell clonal analysis in Paracentrotus lividus digital embryo. Segmentation of cell membranes represented as isosurfaces. a 32-cell stage, b 201-cell stage, c 334-cell stage, and d 545-cell stage. Scale bar 20 μm. e Flat representation of the cell lineage tree. Line segments between branching points represent the cell life time, branching points indicate mitoses. Color map (a-e) given by a set of colors associated with each cell at the 32-cell stage, color propagated along the cell lineage tree and thus revealing cell clones. This representation highlights the fact that very little cell dispersion occurs through the first 10 cell divisions (Reconstructions from live imaging from Rizzi B., unpublished)|
References [+] :