Spatio-temporal dynamics of intercellular Notch signaling: a modeling approach

[eng] Intercellular signalling is a mechanism by which cells communicate and mediate coordinated responses. In this Thesis we perform theoretical and computational analyses to evaluate spatio-temporal organizations that can arise in developing embryos through juxtacrine signalling mediated by Notch...

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Detalles Bibliográficos
Autor: Luna Escalante, Juan Camilo
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/107214
Acceso en línea:https://hdl.handle.net/2445/107214
http://hdl.handle.net/10803/400610
Access Level:acceso abierto
Palabra clave:Proteïnes de membrana
Diferenciació cel·lular
Membrane proteins
Cell diferentiation
Descripción
Sumario:[eng] Intercellular signalling is a mechanism by which cells communicate and mediate coordinated responses. In this Thesis we perform theoretical and computational analyses to evaluate spatio-temporal organizations that can arise in developing embryos through juxtacrine signalling mediated by Notch receptor. Juxtacrine signalling is a type of intercellular communication in which adjacent cells mutually interact through membrane-attached proteins (receptors and ligands). In the case of Notch signalling, the ligands are regulated by the signalling, establishing a feedback loop on the activation of the signal between adjacent cells. Our study focused on the following open questions: 1. What coordinated responses arise when Notch signalling is activated by two (or more) co-expressing ligands? 2. What is the effect on the response mediated by Notch signalling when considering a gene involved in cell differentiation that promotes it on transcription, but in turn is repressed by the signal? 3. Which processes can modulate the signalling efficiency of a ligand? These questions encompass aspects occurring at different levels, ranging from the type of response that arises in a tissue (salt-and-pepper patterning, homogeneous states or propagation of a cell fate in an expansive wave), the signalling state of cells (sending, receiver, among others), up to the dynamics of the intracellular processing of Notch. We used a modelling and computational approach for their study and compared, when possible, with previously reported phenotypes in developing embryos.