Open AccessDeconvolving the roles of Wnt ligands and receptors in sensing and amplification
Author(s) -
Tan Rui Zhen,
Ji Ni,
Mentink Remco A,
Korswagen Hendrik C,
van Oudenaarden Alexander
Publication year - 2013
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2012.64
Subject(s) - biology , multicellular organism , wnt signaling pathway , polarity (international relations) , cell polarity , caenorhabditis elegans , microbiology and biotechnology , frizzled , receptor , cell , computational biology , intracellular , signal transduction , genetics , gene
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.