Investigating spatio-temporal cellular interactions in embryonic morphogenesis by 4D nucleus tracking and systematic comparative analysis - Taking nematodes C. elegans and C. briggsae as examples

Metazoan embryonic morphogenesis is involved with spatio-temporal interactions between cells during embryogenesis from zygote to larva. These regulatory interactions (e.g. active and passive cell motion driven by cytomechanics) contribute to precise, robust and stereotypic embryo patterns among individuals of a species. To in-depth decipher the underlying mechanism and biological function of such interactions, in this work, we used two closely related species Caenorhabditis elegans and Caenorhabditis briggsae as examples and provided a general framework for system-level comparative analysis. We cultured and imaged 11 wild-type embryos in vivo using 3-dimensional time-lapse confocal microscope for each species, with following automatic nucleus-based cell tracking. We quantitatively constructed their normalized and comparable 4D cell-position atlas in silico, including information like each cell's division timing and migration trajectory during embryogenesis from 4- to 350-cell stage. With highly similar cell lineage in both C. elegans and C. briggsae, we compared their division-timing program and cell-arrangement pattern globally and locally, which revealed a turning point of regulation on positional variation among individuals, within one species as well as between two species. Moreover, this down regulation could rescue some cellular positional variation caused by division-order chaos between C. elegans and C. briggsae. Last but not least, the asynchrony of division between sister cells were found to be functional for local positioning of the newborn cells. Our information-rich dataset and the computational analytic methods could facilitate related research in developmental biology, evolutionary biology, and comparative biology.