Establishment of signaling interactions with cellular resolution for every cell cycle of embryogenesis

Long Chen, Vincy Wing Sze Ho, Ming Kin Wong, Xiaotai Huang, Lu Yan Chan, Hon Chun Kaoru Ng, Xiaoliang Ren, Hong Yan, Zhongying ZHAO*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)37-49
Number of pages13
JournalGenetics
Volume209
Issue number1
DOIs
Publication statusPublished - May 2018

Scopus Subject Areas

  • Genetics

User-Defined Keywords

  • C. elegans
  • Cell contact
  • Cell lineage
  • Division asymmetry
  • Notch signaling

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