During metazoan development, cell division paces need to be fine-tuned by developmental regulators to accommodate proper cell fate differentiation and tissue growth. Failures in such tuning may lead to ¬†catastrophe including tumorous growth or abnormal cell death. How cell division paces are coordinated in vivo to accomodate cell fate differentiation or tissue growth during proliferative stage of animal embryogenesis remains poorly understood.

    Study on the temporal control of cell cycle is technically challenging especially during the early development of a metazoan animal when cells are undergoing rapid proliferation. Systematic documentation of live cell divisions manually in a developing animal becomes technically prohibitive due to enormous manpower costs.

    C. elegans embryogenesis provides a superior model to address the issue because of its invariant development, which produces a total of 558 cells within about 14 hours at room temperature. Majority of the cells exit cell cycle and become terminally differentiated before hatching. We have previously developed a series of tools that allow automated tracing of cell divisions and its ancestries/cell lineage as well as automatic extraction of gene expression activities at single cell resolution for every minute, also termed automated lineaging (Bao et al., 2006, Murray et al., 2008) during nematode embryogenesis. A combination of the automated tools with conventional genetic and molecular approaches, a systematic study of temporal control of cell divisions that are coupled with cell fate differentiation becomes feasible in C. elegans. Our eventual goal is to construct the comprehensive regulatory networks that govern tissue formation or organogenesis in the context of metazoan development.

    To this end, we performed a high-content phenotypic screening achieved by RNA interference (RNAi) followed by automated lineaging up to 350-cell stage for over 800 hundred well conserved genes that were known to produce abnormalities during embryogenesis or early larval development when perturbed. This website was developed to host the quantitative molecular and cellular behaviors for both wild type and perturbed embryos and named as Phenics, derived from phenotyping of C. elegans embryo with single cell resolution.

 


How to Cite: Ho VW, Wong MK, An X, Guan D, Shao J, Ng HC, Ren X, He K, Liao J, Ang Y et al: Systems-level quantification of division timing reveals a common genetic architecture controlling asynchrony and fate asymmetry. Molecular systems biology 2015, 11(6):814.

Reference

Bao, Z., Murray, J.I., Boyle, T., Ooi, S.L., Sandel, M.J., and Waterston, R.H. (2006). Automated cell lineage tracing in Caenorhabditis elegans. PNAS 103, 2707-2712.

Murray, J.I., Bao, Z., Boyle, T.J., Boeck, M.E., Mericle, B.L., Nicholas, T.J., Zhao, Z., Sandel, M.J., and Waterston, R.H. (2008). Automated analysis of embryonic gene expression with cellular resolution in C. elegans. Nature methods 5, 703-709.