Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/59244
Title: Competition in notch signaling with cis enriches cell fate decisions
Author: Formosa Jordan, Pau
Ibañes Miguez, Marta
Keywords: Citologia
Embriologia
Proteïnes
Formació de patrons (Física)
Gens
Interacció cel·lular
Cytology
Embryology
Proteins
Pattern formation (Physical sciences)
Genes
Cell interaction
Issue Date: 29-Apr-2014
Publisher: Public Library of Science (PLoS)
Abstract: Notch signaling is involved in cell fate choices during the embryonic development of Metazoa. Commonly, Notch signaling arises from the binding of the Notch receptor to its ligands in adjacent cells driving cell-to-cell communication. Yet, cell-autonomous control of Notch signaling through both ligand-dependent and ligand-independent mechanisms is known to occur as well. Examples include Notch signaling arising in the absence of ligand binding, and cis-inhibition of Notch signaling by titration of the Notch receptor upon binding to its ligands within a single cell. Increasing experimental evidences support that the binding of the Notch receptor with its ligands within a cell (cis-interactions) can also trigger a cell-autonomous Notch signal (cis-signaling), whose potential effects on cell fate decisions and patterning remain poorly understood. To address this question, herein we mathematically and computationally investigate the cell states arising from the combination of cis-signaling with additional Notch signaling sources, which are either cell-autonomous or involve cell-to-cell communication. Our study shows that cis-signaling can switch from driving cis-activation to effectively perform cis-inhibition and identifies under which conditions this switch occurs. This switch relies on the competition between Notch signaling sources, which share the same receptor but differ in their signaling efficiency. We propose that the role of cis-interactions and their signaling on fine-grained patterning and cell fate decisions is dependent on whether they drive cis-inhibition or cis-activation, which could be controlled during development. Specifically, cis-inhibition and not cis-activation facilitates patterning and enriches it by modulating the ratio of cells in the high-ligand expression state, by enabling additional periodic patterns like stripes and by allowing localized patterning highly sensitive to the precursor state and cell-autonomous bistability. Our study exemplifies the complexity of regulations when multiple signalng sources share the same receptor and provides the tools for their characterization.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0095744
It is part of: PLoS One, 2014, vol. 9, num. 4, p. 1-14
Related resource: http://dx.doi.org/10.1371/journal.pone.0095744
URI: http://hdl.handle.net/2445/59244
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Física Quàntica i Astrofísica)

Files in This Item:
File Description SizeFormat 
643747.pdf2.1 MBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons