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dc.contributor.author | Rodrigo, Guillermo | es_ES |
dc.contributor.author | Elena Fito, Santiago Fco | es_ES |
dc.date.accessioned | 2013-04-30T14:09:42Z | |
dc.date.available | 2013-04-30T14:09:42Z | |
dc.date.issued | 2011-02-14 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10251/28359 | |
dc.description.abstract | Signaling pathways are interconnected to regulatory circuits for sensing the environment and expressing the appropriate genetic profile. In particular, gradients of diffusing molecules (morphogens) determine cell fate at a given position, dictating development and spatial organization. The feedforward loop (FFL) circuit is among the simplest genetic architectures able to generate one-stripe patterns by operating as an amplitude detection device, where high output levels are achieved at intermediate input ones. Here, using a heuristic optimization-based approach, we dissected the design space containing all possible topologies and parameter values of the FFL circuits. We explored the ability of being sensitive or adaptive to variations in the critical morphogen level where cell fate is switched. We found four different solutions for precision, corresponding to the four incoherent architectures, but remarkably only one mode for adaptiveness, the incoherent type 4 (I4-FFL). We further carried out a theoretical study to unveil the design principle for such structural discrimination, finding that the synergistic action and cooperative binding on the downstream promoter are instrumental to achieve absolute adaptive responses. Subsequently, we analyzed the robustness of these optimal circuits against perturbations in the kinetic parameters and molecular noise, which has allowed us to depict a scenario where adaptiveness, parameter sensitivity and noise tolerance are different, correlated facets of the robustness of the I4-FFL circuit. Strikingly, we showed a strong correlation between the input (environment-related) and the intrinsic (mutation-related) susceptibilities. Finally, we discussed the evolution of incoherent regulations in terms of multifunctionality and robustness. | es_ES |
dc.description.sponsorship | This work was supported by the Spanish Ministerio de Ciencia e Innovacion grant BFU-2009-06993. GR is the recipient of a graduate fellowship from the Generalitat Valenciana (BFPI-2007-160). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | en_EN |
dc.language | Inglés | es_ES |
dc.publisher | Public Library of Science | es_ES |
dc.relation.ispartof | PLoS ONE | es_ES |
dc.rights | Reconocimiento (by) | es_ES |
dc.title | Structural discrimination of robustness in transcriptional feedforward loops for pattern formation | es_ES |
dc.type | Artículo | es_ES |
dc.identifier.doi | 10.1371/journal.pone.0016904 | |
dc.relation.projectID | info:eu-repo/grantAgreement/MICINN//BFU2009-06993/ES/Biologia Evolutiva Y De Sistemas De La Emergencia De Fitovirus De Rna/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/GVA//BFPI-2007-160/ | es_ES |
dc.rights.accessRights | Abierto | es_ES |
dc.contributor.affiliation | Universitat Politècnica de València. Instituto Universitario Mixto de Biología Molecular y Celular de Plantas - Institut Universitari Mixt de Biologia Molecular i Cel·lular de Plantes | es_ES |
dc.description.bibliographicCitation | Rodrigo, G.; Elena Fito, SF. (2011). Structural discrimination of robustness in transcriptional feedforward loops for pattern formation. PLoS ONE. 6:16904-16904. https://doi.org/10.1371/journal.pone.0016904 | es_ES |
dc.description.accrualMethod | S | es_ES |
dc.relation.publisherversion | http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016904 | es_ES |
dc.description.upvformatpinicio | 16904 | es_ES |
dc.description.upvformatpfin | 16904 | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | es_ES |
dc.description.volume | 6 | es_ES |
dc.relation.senia | 218181 | |
dc.identifier.pmid | 21340024 | en_EN |
dc.identifier.pmcid | PMC3038866 | en_EN |
dc.contributor.funder | Generalitat Valenciana | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación | es_ES |
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