Spatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary.

The isthmic organizer mediating differentiation of mid- and hindbrain during vertebrate development is characterized by a well-defined pattern of locally restricted gene expression domains around the mid-hindbrain boundary (MHB). This pattern is established and maintained by a regulatory network bet...

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Autores principales:	Dominik M Wittmann, Florian Blöchl, Dietrich Trümbach, Wolfgang Wurst, Nilima Prakash, Fabian J Theis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4064ba97b37e44dbb0fe54488c33b5e8
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spelling	oai:doaj.org-article:4064ba97b37e44dbb0fe54488c33b5e82021-11-25T05:42:50ZSpatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary.1553-734X1553-735810.1371/journal.pcbi.1000569https://doaj.org/article/4064ba97b37e44dbb0fe54488c33b5e82009-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19936059/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The isthmic organizer mediating differentiation of mid- and hindbrain during vertebrate development is characterized by a well-defined pattern of locally restricted gene expression domains around the mid-hindbrain boundary (MHB). This pattern is established and maintained by a regulatory network between several transcription and secreted factors that is not yet understood in full detail. In this contribution we show that a Boolean analysis of the characteristic spatial gene expression patterns at the murine MHB reveals key regulatory interactions in this network. Our analysis employs techniques from computational logic for the minimization of Boolean functions. This approach allows us to predict also the interplay of the various regulatory interactions. In particular, we predict a maintaining, rather than inducing, effect of Fgf8 on Wnt1 expression, an issue that remained unclear from published data. Using mouse anterior neural plate/tube explant cultures, we provide experimental evidence that Fgf8 in fact only maintains but does not induce ectopic Wnt1 expression in these explants. In combination with previously validated interactions, this finding allows for the construction of a regulatory network between key transcription and secreted factors at the MHB. Analyses of Boolean, differential equation and reaction-diffusion models of this network confirm that it is indeed able to explain the stable maintenance of the MHB as well as time-courses of expression patterns both under wild-type and various knock-out conditions. In conclusion, we demonstrate that similar to temporal also spatial expression patterns can be used to gain information about the structure of regulatory networks. We show, in particular, that the spatial gene expression patterns around the MHB help us to understand the maintenance of this boundary on a systems level.Dominik M WittmannFlorian BlöchlDietrich TrümbachWolfgang WurstNilima PrakashFabian J TheisPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 5, Iss 11, p e1000569 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Dominik M Wittmann Florian Blöchl Dietrich Trümbach Wolfgang Wurst Nilima Prakash Fabian J Theis Spatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary.
description	The isthmic organizer mediating differentiation of mid- and hindbrain during vertebrate development is characterized by a well-defined pattern of locally restricted gene expression domains around the mid-hindbrain boundary (MHB). This pattern is established and maintained by a regulatory network between several transcription and secreted factors that is not yet understood in full detail. In this contribution we show that a Boolean analysis of the characteristic spatial gene expression patterns at the murine MHB reveals key regulatory interactions in this network. Our analysis employs techniques from computational logic for the minimization of Boolean functions. This approach allows us to predict also the interplay of the various regulatory interactions. In particular, we predict a maintaining, rather than inducing, effect of Fgf8 on Wnt1 expression, an issue that remained unclear from published data. Using mouse anterior neural plate/tube explant cultures, we provide experimental evidence that Fgf8 in fact only maintains but does not induce ectopic Wnt1 expression in these explants. In combination with previously validated interactions, this finding allows for the construction of a regulatory network between key transcription and secreted factors at the MHB. Analyses of Boolean, differential equation and reaction-diffusion models of this network confirm that it is indeed able to explain the stable maintenance of the MHB as well as time-courses of expression patterns both under wild-type and various knock-out conditions. In conclusion, we demonstrate that similar to temporal also spatial expression patterns can be used to gain information about the structure of regulatory networks. We show, in particular, that the spatial gene expression patterns around the MHB help us to understand the maintenance of this boundary on a systems level.
format	article
author	Dominik M Wittmann Florian Blöchl Dietrich Trümbach Wolfgang Wurst Nilima Prakash Fabian J Theis
author_facet	Dominik M Wittmann Florian Blöchl Dietrich Trümbach Wolfgang Wurst Nilima Prakash Fabian J Theis
author_sort	Dominik M Wittmann
title	Spatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary.
title_short	Spatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary.
title_full	Spatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary.
title_fullStr	Spatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary.
title_full_unstemmed	Spatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary.
title_sort	spatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/4064ba97b37e44dbb0fe54488c33b5e8
work_keys_str_mv	AT dominikmwittmann spatialanalysisofexpressionpatternspredictsgeneticinteractionsatthemidhindbrainboundary AT florianblochl spatialanalysisofexpressionpatternspredictsgeneticinteractionsatthemidhindbrainboundary AT dietrichtrumbach spatialanalysisofexpressionpatternspredictsgeneticinteractionsatthemidhindbrainboundary AT wolfgangwurst spatialanalysisofexpressionpatternspredictsgeneticinteractionsatthemidhindbrainboundary AT nilimaprakash spatialanalysisofexpressionpatternspredictsgeneticinteractionsatthemidhindbrainboundary AT fabianjtheis spatialanalysisofexpressionpatternspredictsgeneticinteractionsatthemidhindbrainboundary
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Spatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary.

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