Operating principles of Notch–Delta–Jagged module of cell–cell communication
Notch pathway is an evolutionarily conserved cell–cell communication mechanism governing cell-fate during development and tumor progression. It is activated when Notch receptor of one cell binds to either of its ligand—Delta or Jagged—of another cell. Notch–Delta (ND) signaling forms a two-way switc...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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IOP Publishing
2015-01-01
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| Series: | New Journal of Physics |
| Subjects: | |
| Online Access: | https://doi.org/10.1088/1367-2630/17/5/055021 |
| _version_ | 1827873942175481856 |
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| author | Mohit Kumar Jolly Marcelo Boareto Mingyang Lu Jose’ N Onuchic Cecilia Clementi Eshel Ben-Jacob |
| author_facet | Mohit Kumar Jolly Marcelo Boareto Mingyang Lu Jose’ N Onuchic Cecilia Clementi Eshel Ben-Jacob |
| author_sort | Mohit Kumar Jolly |
| collection | DOAJ |
| description | Notch pathway is an evolutionarily conserved cell–cell communication mechanism governing cell-fate during development and tumor progression. It is activated when Notch receptor of one cell binds to either of its ligand—Delta or Jagged—of another cell. Notch–Delta (ND) signaling forms a two-way switch, and two cells interacting via ND signaling adopt different fates—Sender (high ligand, low receptor) and Receiver (low ligand, high receptor). Notch–Delta–Jagged signaling (NDJ) behaves as a three-way switch and enables an additional fate—hybrid Sender/Receiver (S/R) (medium ligand, medium receptor). Here, by extending our framework of NDJ signaling for a two-cell system, we show that higher production rate of Jagged, but not that of Delta, expands the range of parameters for which both cells attain the hybrid S/R state. Conversely, glycosyltransferase Fringe and cis -inhibition reduces this range of conditions, and reduces the relative stability of the hybrid S/R state, thereby promoting cell-fate divergence and consequently lateral inhibition-based patterns. Lastly, soluble Jagged drives the cells to attain the hybrid S/R state, and soluble Delta drives them to be Receivers. We also discuss the critical role of hybrid S/R state in promoting cancer metastasis by enabling collective cell migration and expanding cancer stem cell (CSC) population. |
| first_indexed | 2024-03-12T16:44:09Z |
| format | Article |
| id | doaj.art-0a3ffc0241644ff387e9dc9b3c797c0d |
| institution | Directory Open Access Journal |
| issn | 1367-2630 |
| language | English |
| last_indexed | 2024-03-12T16:44:09Z |
| publishDate | 2015-01-01 |
| publisher | IOP Publishing |
| record_format | Article |
| series | New Journal of Physics |
| spelling | doaj.art-0a3ffc0241644ff387e9dc9b3c797c0d2023-08-08T14:17:53ZengIOP PublishingNew Journal of Physics1367-26302015-01-0117505502110.1088/1367-2630/17/5/055021Operating principles of Notch–Delta–Jagged module of cell–cell communicationMohit Kumar Jolly0Marcelo Boareto1Mingyang Lu2Jose’ N Onuchic3Cecilia Clementi4Eshel Ben-Jacob5Center for Theoretical Biological Physics, Rice University , Houston, TX 77005-1827, USA; Department of Bioengineering, Rice University , Houston, TX 77005-1827, USACenter for Theoretical Biological Physics, Rice University , Houston, TX 77005-1827, USA; Institute of Physics, University of Sao Paulo , Sao Paulo 05508, BrazilCenter for Theoretical Biological Physics, Rice University , Houston, TX 77005-1827, USACenter for Theoretical Biological Physics, Rice University , Houston, TX 77005-1827, USA; Department of Chemistry, Rice University , Houston, TX 77005-1827, USA; Department of Physics and Astronomy, Rice University , Houston, TX 77005-1827, USA; Department of Biosciences, Rice University , Houston, TX 77005-1827, USACenter for Theoretical Biological Physics, Rice University , Houston, TX 77005-1827, USA; Department of Chemistry, Rice University , Houston, TX 77005-1827, USACenter for Theoretical Biological Physics, Rice University , Houston, TX 77005-1827, USA; Department of Biosciences, Rice University , Houston, TX 77005-1827, USA; School of Physics and Astronomy and The Sagol School of Neuroscience, Tel-Aviv University , Tel-Aviv 69978, IsraelNotch pathway is an evolutionarily conserved cell–cell communication mechanism governing cell-fate during development and tumor progression. It is activated when Notch receptor of one cell binds to either of its ligand—Delta or Jagged—of another cell. Notch–Delta (ND) signaling forms a two-way switch, and two cells interacting via ND signaling adopt different fates—Sender (high ligand, low receptor) and Receiver (low ligand, high receptor). Notch–Delta–Jagged signaling (NDJ) behaves as a three-way switch and enables an additional fate—hybrid Sender/Receiver (S/R) (medium ligand, medium receptor). Here, by extending our framework of NDJ signaling for a two-cell system, we show that higher production rate of Jagged, but not that of Delta, expands the range of parameters for which both cells attain the hybrid S/R state. Conversely, glycosyltransferase Fringe and cis -inhibition reduces this range of conditions, and reduces the relative stability of the hybrid S/R state, thereby promoting cell-fate divergence and consequently lateral inhibition-based patterns. Lastly, soluble Jagged drives the cells to attain the hybrid S/R state, and soluble Delta drives them to be Receivers. We also discuss the critical role of hybrid S/R state in promoting cancer metastasis by enabling collective cell migration and expanding cancer stem cell (CSC) population.https://doi.org/10.1088/1367-2630/17/5/055021notch signalingmultistabilityjaggedsender/receivercell–cell communicationpattern formation |
| spellingShingle | Mohit Kumar Jolly Marcelo Boareto Mingyang Lu Jose’ N Onuchic Cecilia Clementi Eshel Ben-Jacob Operating principles of Notch–Delta–Jagged module of cell–cell communication New Journal of Physics notch signaling multistability jagged sender/receiver cell–cell communication pattern formation |
| title | Operating principles of Notch–Delta–Jagged module of cell–cell communication |
| title_full | Operating principles of Notch–Delta–Jagged module of cell–cell communication |
| title_fullStr | Operating principles of Notch–Delta–Jagged module of cell–cell communication |
| title_full_unstemmed | Operating principles of Notch–Delta–Jagged module of cell–cell communication |
| title_short | Operating principles of Notch–Delta–Jagged module of cell–cell communication |
| title_sort | operating principles of notch delta jagged module of cell cell communication |
| topic | notch signaling multistability jagged sender/receiver cell–cell communication pattern formation |
| url | https://doi.org/10.1088/1367-2630/17/5/055021 |
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