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 maintai...

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Main Authors: Rui Zhen Tan, Ni Ji, Remco A Mentink, Hendrik C Korswagen, Alexander van Oudenaarden
Format: Article
Language:English
Published: Springer Nature 2013-01-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.1038/msb.2012.64
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author Rui Zhen Tan
Ni Ji
Remco A Mentink
Hendrik C Korswagen
Alexander van Oudenaarden
author_facet Rui Zhen Tan
Ni Ji
Remco A Mentink
Hendrik C Korswagen
Alexander van Oudenaarden
author_sort Rui Zhen Tan
collection DOAJ
description 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.
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series Molecular Systems Biology
spelling doaj-art-58bb46cb8c8c4883bc0febea1233036a2025-08-20T03:46:34ZengSpringer NatureMolecular Systems Biology1744-42922013-01-019111110.1038/msb.2012.64Deconvolving the roles of Wnt ligands and receptors in sensing and amplificationRui Zhen Tan0Ni Ji1Remco A Mentink2Hendrik C Korswagen3Alexander van Oudenaarden4Harvard University Graduate Biophysics Program, Harvard Medical SchoolDepartment of Brian and Cognitive Sciences, Massachusetts Institute of TechnologyHubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center UtrechtHubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center UtrechtHubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center UtrechtAbstract 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.https://doi.org/10.1038/msb.2012.64Caenorhabditis eleganscell polarityphenomenological modelingWnt signaling
spellingShingle Rui Zhen Tan
Ni Ji
Remco A Mentink
Hendrik C Korswagen
Alexander van Oudenaarden
Deconvolving the roles of Wnt ligands and receptors in sensing and amplification
Molecular Systems Biology
Caenorhabditis elegans
cell polarity
phenomenological modeling
Wnt signaling
title Deconvolving the roles of Wnt ligands and receptors in sensing and amplification
title_full Deconvolving the roles of Wnt ligands and receptors in sensing and amplification
title_fullStr Deconvolving the roles of Wnt ligands and receptors in sensing and amplification
title_full_unstemmed Deconvolving the roles of Wnt ligands and receptors in sensing and amplification
title_short Deconvolving the roles of Wnt ligands and receptors in sensing and amplification
title_sort deconvolving the roles of wnt ligands and receptors in sensing and amplification
topic Caenorhabditis elegans
cell polarity
phenomenological modeling
Wnt signaling
url https://doi.org/10.1038/msb.2012.64
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