Establishment of Signaling Interactions with Cellular Resolution for Every Cell Cycle of Embryogenesis

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

article

Long Chen¹  Vincy Wing Sze Ho²  Ming-Kin Wong²  Xiaotai Huang³  Lu-yan Chan²  Hon Chun Kaoru Ng²  Xiaoliang Ren²  Hong Yan¹  Zhongying Zhao² 

[1] Department of Electronic Engineering, City University of Hong Kong, China;Department of Biology, Hong Kong Baptist University, China;School of Computer Science and Technology, Xidian University, Xi’an, 710126 China;State Key Laboratory of Environmental and Biological Analysis, Hong Kong Baptist University, China

关键词: Cell contact;    Notch signaling;    cell lineage;    C. elegans;    division asymmetry;   

DOI  :  10.1534/genetics.118.300820

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

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.

【 授权许可】

CC BY