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:	Clare E Giacomantonio, Geoffrey J Goodhill
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b40d307bf96643bfa9d3db15aa72b1e8
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id	oai:doaj.org-article:b40d307bf96643bfa9d3db15aa72b1e8
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spelling	oai:doaj.org-article:b40d307bf96643bfa9d3db15aa72b1e82021-11-18T05:49:18ZA Boolean model of the gene regulatory network underlying Mammalian cortical area development.1553-734X1553-735810.1371/journal.pcbi.1000936https://doaj.org/article/b40d307bf96643bfa9d3db15aa72b1e82010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20862356/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The 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 possible networks containing the five genes of interest. We found that only 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.Clare E GiacomantonioGeoffrey J GoodhillPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 6, Iss 9 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Clare E Giacomantonio Geoffrey J Goodhill A Boolean model of the gene regulatory network underlying Mammalian cortical area development.
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 possible networks containing the five genes of interest. We found that only 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.
format	article
author	Clare E Giacomantonio Geoffrey J Goodhill
author_facet	Clare E Giacomantonio Geoffrey J Goodhill
author_sort	Clare E Giacomantonio
title	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_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_sort	boolean model of the gene regulatory network underlying mammalian cortical area development.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/b40d307bf96643bfa9d3db15aa72b1e8
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A Boolean model of the gene regulatory network underlying Mammalian cortical area development.

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