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A Boolean Model of the Gene Regulatory Network Underlying Mammalian Cortical Area Development

The cerebral cortex is divided into many functionally distinct areas. The emergence of these areas during neural development is dependent on the expression patterns of several genes. Along the anterior-posterior axis, gradients of Fgf8, Emx2, Pax6, Coup-tfi, and Sp8 play a particularly strong role i...

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Autores principales: Giacomantonio, Clare E., Goodhill, Geoffrey J.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940723/
https://www.ncbi.nlm.nih.gov/pubmed/20862356
http://dx.doi.org/10.1371/journal.pcbi.1000936
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author Giacomantonio, Clare E.
Goodhill, Geoffrey J.
author_facet Giacomantonio, Clare E.
Goodhill, Geoffrey J.
author_sort Giacomantonio, Clare E.
collection PubMed
description The cerebral cortex is divided into many functionally distinct areas. The emergence of these areas during neural development is dependent on the expression patterns of several genes. Along the anterior-posterior axis, gradients of Fgf8, Emx2, Pax6, Coup-tfi, and Sp8 play a particularly strong role in specifying areal identity. However, our understanding of the regulatory interactions between these genes that lead to their confinement to particular spatial patterns is currently qualitative and incomplete. We therefore used a computational model of the interactions between these five genes to determine which interactions, and combinations of interactions, occur in networks that reproduce the anterior-posterior expression patterns observed experimentally. The model treats expression levels as Boolean, reflecting the qualitative nature of the expression data currently available. We simulated gene expression patterns created by all [Image: see text] possible networks containing the five genes of interest. We found that only [Image: see text] of these networks were able to reproduce the experimentally observed expression patterns. These networks all lacked certain interactions and combinations of interactions including auto-regulation and inductive loops. Many higher order combinations of interactions also never appeared in networks that satisfied our criteria for good performance. While there was remarkable diversity in the structure of the networks that perform well, an analysis of the probability of each interaction gave an indication of which interactions are most likely to be present in the gene network regulating cortical area development. We found that in general, repressive interactions are much more likely than inductive ones, but that mutually repressive loops are not critical for correct network functioning. Overall, our model illuminates the design principles of the gene network regulating cortical area development, and makes novel predictions that can be tested experimentally.
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spelling pubmed-29407232010-09-22 A Boolean Model of the Gene Regulatory Network Underlying Mammalian Cortical Area Development Giacomantonio, Clare E. Goodhill, Geoffrey J. PLoS Comput Biol Research Article The cerebral cortex is divided into many functionally distinct areas. The emergence of these areas during neural development is dependent on the expression patterns of several genes. Along the anterior-posterior axis, gradients of Fgf8, Emx2, Pax6, Coup-tfi, and Sp8 play a particularly strong role in specifying areal identity. However, our understanding of the regulatory interactions between these genes that lead to their confinement to particular spatial patterns is currently qualitative and incomplete. We therefore used a computational model of the interactions between these five genes to determine which interactions, and combinations of interactions, occur in networks that reproduce the anterior-posterior expression patterns observed experimentally. The model treats expression levels as Boolean, reflecting the qualitative nature of the expression data currently available. We simulated gene expression patterns created by all [Image: see text] possible networks containing the five genes of interest. We found that only [Image: see text] of these networks were able to reproduce the experimentally observed expression patterns. These networks all lacked certain interactions and combinations of interactions including auto-regulation and inductive loops. Many higher order combinations of interactions also never appeared in networks that satisfied our criteria for good performance. While there was remarkable diversity in the structure of the networks that perform well, an analysis of the probability of each interaction gave an indication of which interactions are most likely to be present in the gene network regulating cortical area development. We found that in general, repressive interactions are much more likely than inductive ones, but that mutually repressive loops are not critical for correct network functioning. Overall, our model illuminates the design principles of the gene network regulating cortical area development, and makes novel predictions that can be tested experimentally. Public Library of Science 2010-09-16 /pmc/articles/PMC2940723/ /pubmed/20862356 http://dx.doi.org/10.1371/journal.pcbi.1000936 Text en Giacomantonio, Goodhill. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Giacomantonio, Clare E.
Goodhill, Geoffrey J.
A Boolean Model of the Gene Regulatory Network Underlying Mammalian Cortical Area Development
title A Boolean Model of the Gene Regulatory Network Underlying Mammalian Cortical Area Development
title_full A Boolean Model of the Gene Regulatory Network Underlying Mammalian Cortical Area Development
title_fullStr A Boolean Model of the Gene Regulatory Network Underlying Mammalian Cortical Area Development
title_full_unstemmed A Boolean Model of the Gene Regulatory Network Underlying Mammalian Cortical Area Development
title_short A Boolean Model of the Gene Regulatory Network Underlying Mammalian Cortical Area Development
title_sort boolean model of the gene regulatory network underlying mammalian cortical area development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940723/
https://www.ncbi.nlm.nih.gov/pubmed/20862356
http://dx.doi.org/10.1371/journal.pcbi.1000936
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