title: Deconvolving the roles of Wnt ligands and receptors in sensing and amplification.
abstract: Establishment of cell polarity is crucial for many biological processes including cell migration and asymmetric cell division. The establishment of cell polarity consists of two sequential processes: an external gradient is first sensed and then the resulting signal is amplified and maintained by intracellular signaling networks usually using positive feedback regulation. Generally, these two processes are intertwined and it is challenging to determine which proteins contribute to the sensing or amplification process, particularly in multicellular organisms. Here, we integrated phenomenological modeling with quantitative single-cell measurements to separate the sensing and amplification components of Wnt ligands and receptors during establishment of polarity of the Caenorhabditis elegans P cells. By systematically exploring how P-cell polarity is altered in Wnt ligand and receptor mutants, we inferred that ligands predominantly affect the sensing process, whereas receptors are needed for both sensing and amplification. This integrated approach is generally applicable to other systems and will facilitate decoupling of the different layers of signal sensing and amplification.
authors.affiliation: Harvard University Graduate Biophysics Program, Harvard Medical School, Boston, MA, USA.
authors.forename: Rui Zhen
authors.initials: RZ
authors.lastname: Tan
authors.forename: Ni
authors.initials: N
authors.lastname: Ji
authors.forename: Remco A
authors.initials: RA
authors.lastname: Mentink
authors.forename: Hendrik C
authors.initials: HC
authors.lastname: Korswagen
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D060490:Receptors, Wnt / Q000235:genetics / Q000378:metabolism*; D059010:Single-Cell Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C117259:Egl-20 protein, C elegans; D006023:Glycoproteins; D008565:Membrane Proteins; C108315:Mom-5 protein, C elegans; D060490:Receptors, Wnt; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C086488:lag-2 protein, C elegans; C081464:lin-31 protein, C elegans