Towards 3D in silico modeling of the sea urchin embryonic development
Journal of chemical biology
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
... f 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 We show, with some unpublished results, how the proposed methodology can be applied to sea urchin species that have been model organisms in the field of classical embryology and modern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. Keywords Morphogenesis . Sea urchin . Cellular dynamics . In vivo imaging . Multiscale digital specimens . In silico modeling The phenomenological and theoretical reconstruction of multiscale dynamics in animal embryogenesis: a general perspective In an ideal scenario, morphogenetic events could be understood through a circular path integrating quantitative reconstructions, data analysis, and modeling (depicted in Fig. 1) . The bottom-up digital reconstruction and analysis from the sub-cellular scale to the whole embryo level should be combined with a top-down approach. The latter includes the effect of high-level phenotypic features, such as tissue biomechanics on biochemical processes and on the regulation of gene expression. Events at the subcellular level modify the properties of cells and extracellular matrices, and the latter, in turn, modulates the biochemical activity of the cell [13, 74] . Among all possible genetically and epigenetically encoded processes, cells divide, differentiate, and migrate in the context of their self-produced external environment [67, 102] . Cell features over time can be described with a set of parameters including the cell position, cell lineage, volume, surface, shape indexes, local convexity or concavity, nuclear/ cytoplasmic ratio, cell neighborhood and surface of contact, cell polarization assessed by the asymmetric distribution of sub-cellular structures, intrinsic motility, and directionality. At the mesoscopic level, tissue patterning depends on cell displacements, cell-cell adhesion, and cell division characteristics. The emergence of the most macroscopic features shapes the whole embryo and provides global mechanical constraints.