The invariant development and transparent body of the nematode Caenorhabditis elegans enables complete delineation of cell lineages throughout development. Despite extensive studies of cell division, cell migration and cell fate differentiation, cell morphology during development has not yet been systematically characterized in any metazoan, including C. elegans. This knowledge gap substantially hampers many studies in both developmental and cell biology. Here we report an automatic pipeline, CShaper, which combines automated segmentation of fluorescently labeled membranes with automated cell lineage tracing. We apply this pipeline to quantify morphological parameters of densely packed cells in 17 developing C. elegans embryos. Consequently, we generate a time-lapse 3D atlas of cell morphology for the C. elegans embryo from the 4- to 350-cell stages, including cell shape, volume, surface area, migration, nucleus position and cell-cell contact with resolved cell identities. We anticipate that CShaper and the morphological atlas will stimulate and enhance further studies in the fields of developmental biology, cell biology and biomechanics.

Coordination of cell division timing is crucial for proper cell fate specification and tissue growth. However, the differential regulation of cell division timing across or within cell types during metazoan development remains poorly understood. To elucidate the systems-level genetic architecture coordinating division timing, we performed a high-content screening for genes whose depletion produced a significant reduction in the asynchrony of division between sister cells (ADS) compared to that of wild-type during Caenorhabditis elegans embryogenesis. We quantified division timing using 3D time-lapse imaging followed by computer-aided lineage analysis. A total of 822 genes were selected for perturbation based on their conservation and known roles in development. Surprisingly, we find that cell fate determinants are not only essential for establishing fate asymmetry, but also are imperative for setting the ADS regardless of cellular context, indicating a common genetic architecture used by both cellular processes. The fate determinants demonstrate either coupled or separate regulation between the two processes. The temporal coordination appears to facilitate cell migration during fate specification or tissue growth. Our quantitative dataset with cellular resolution provides a resource for future analyses of the genetic control of spatial and temporal coordination during metazoan development.

Background: NHR-25 and ELT-3 are required for development but not for initial specification of epidermis in C. elegans. Results: Genome-wide in vivo targets of NHR-25 are identified. Conclusion: NHR-25 and ELT-3 collaboratively regulate development but differentially control metabolism of epidermis. Significance: The results provide insight into how tissue-specific transcription factors enforce cell fate specification initiated by its master regulator.

Background Understanding the cellular architecture is a fundamental problem in various biological studies. C. elegans is widely used as a model organism in these studies because of its unique fate determinations. In recent years, researchers have worked extensively on C. elegans to excavate the regulations of genes and proteins on cell mobility and communication. Although various algorithms have been proposed to analyze nucleus, cell shape features are not yet well recorded. This paper proposes a method to systematically analyze three-dimensional morphological cellular features. Results Three-dimensional Membrane Morphological Segmentation (3DMMS) makes use of several novel techniques, such as statistical intensity normalization, and region filters, to pre-process the cell images. We then segment membrane stacks based on watershed algorithms. 3DMMS achieves high robustness and precision over different time points (development stages). It is compared with two state-of-the-art algorithms, RACE and BCOMS. Quantitative analysis shows 3DMMS performs best with the average Dice ratio of 97.7% at six time points. In addition, 3DMMS also provides time series of internal and external shape features of C. elegans . Conclusion We have developed the 3DMMS based technique for embryonic shape reconstruction at the single-cell level. With cells accurately segmented, 3DMMS makes it possible to study cellular shapes and bridge morphological features and biological expression in embryo research. Electronic supplementary material The online version of this article (10.1186/s12859-019-2720-x) contains supplementary material, which is available to authorized users.

Intercellular signaling interactions play a key role in breaking fate symmetry during animal development. Identification of signaling interactions at cellular resolution is technically challenging, especially in a developing embryo. Here, we develop a platform that allows automated inference and validation of signaling interactions for every cell cycle of Caenorhabditis elegans embryogenesis. This is achieved by the generation of a systems-level cell contact map, which consists of 1114 highly confident intercellular contacts, by modeling analysis and is validated through cell membrane labeling coupled with cell lineage analysis. We apply the map to identify cell pairs between which a Notch signaling interaction takes place. By generating expression patterns for two ligands and two receptors of the Notch signaling pathway with cellular resolution using the automated expression profiling technique, we are able to refine existing and identify novel Notch interactions during C. elegans embryogenesis. Targeted cell ablation followed by cell lineage analysis demonstrates the roles of signaling interactions during cell division in breaking fate symmetry. Finally, we describe the development of a website that allows online access to the cell-cell contact map for mapping of other signaling interactions by the community. The platform can be adapted to establish cellular interactions from any other signaling pathway.