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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| Format: | Article |
| Language: | English |
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Springer Nature
2013-01-01
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| Series: | Molecular Systems Biology |
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| 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. |
| format | Article |
| id | doaj-art-58bb46cb8c8c4883bc0febea1233036a |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| 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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