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000136030 0247_ $$2doi$$a10.1371/journal.pcbi.1000569
000136030 0247_ $$2pmid$$apmid:19936059
000136030 0247_ $$2pmc$$apmc:PMC2774268
000136030 0247_ $$2ISSN$$a1553-734X
000136030 0247_ $$2ISSN$$a1553-7358
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000136030 037__ $$aDZNE-2020-02352
000136030 041__ $$aEnglish
000136030 082__ $$a610
000136030 1001_ $$0P:(DE-HGF)0$$aWittmann, Dominik M$$b0
000136030 245__ $$aSpatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary.
000136030 260__ $$aSan Francisco, Calif.$$bPublic Library of Science$$c2009
000136030 264_1 $$2Crossref$$3online$$bPublic Library of Science (PLoS)$$c2009-11-20
000136030 3367_ $$2DRIVER$$aarticle
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000136030 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1713863109_10934
000136030 3367_ $$2BibTeX$$aARTICLE
000136030 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000136030 3367_ $$00$$2EndNote$$aJournal Article
000136030 520__ $$aThe 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.
000136030 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000136030 542__ $$2Crossref$$i2009-11-20$$uhttp://creativecommons.org/licenses/by/4.0/
000136030 588__ $$aDataset connected to CrossRef, PubMed,
000136030 650_7 $$2NLM Chemicals$$aFgf8 protein, mouse
000136030 650_7 $$2NLM Chemicals$$aWnt1 Protein
000136030 650_7 $$2NLM Chemicals$$aWnt1 protein, mouse
000136030 650_7 $$0148997-75-5$$2NLM Chemicals$$aFibroblast Growth Factor 8
000136030 650_2 $$2MeSH$$aAlgorithms
000136030 650_2 $$2MeSH$$aAnimals
000136030 650_2 $$2MeSH$$aBrain: embryology
000136030 650_2 $$2MeSH$$aBrain: metabolism
000136030 650_2 $$2MeSH$$aBrain Mapping: methods
000136030 650_2 $$2MeSH$$aComputational Biology: methods
000136030 650_2 $$2MeSH$$aDiffusion
000136030 650_2 $$2MeSH$$aFibroblast Growth Factor 8: genetics
000136030 650_2 $$2MeSH$$aGene Expression Profiling: methods
000136030 650_2 $$2MeSH$$aGene Expression Regulation, Developmental
000136030 650_2 $$2MeSH$$aMice
000136030 650_2 $$2MeSH$$aMice, Inbred C57BL
000136030 650_2 $$2MeSH$$aModels, Biological
000136030 650_2 $$2MeSH$$aModels, Statistical
000136030 650_2 $$2MeSH$$aTranscription, Genetic
000136030 650_2 $$2MeSH$$aWnt1 Protein: genetics
000136030 7001_ $$0P:(DE-HGF)0$$aBlöchl, Florian$$b1
000136030 7001_ $$0P:(DE-2719)9000367$$aTrümbach, Dietrich$$b2$$udzne
000136030 7001_ $$0P:(DE-2719)2000028$$aWurst, Wolfgang$$b3$$udzne
000136030 7001_ $$0P:(DE-2719)9000256$$aPrakash, Nilima$$b4$$udzne
000136030 7001_ $$0P:(DE-HGF)0$$aTheis, Fabian J$$b5$$eCorresponding author
000136030 77318 $$2Crossref$$3journal-article$$a10.1371/journal.pcbi.1000569$$b : Public Library of Science (PLoS), 2009-11-20$$n11$$pe1000569$$tPLoS Computational Biology$$v5$$x1553-7358$$y2009
000136030 773__ $$0PERI:(DE-600)2193340-6$$a10.1371/journal.pcbi.1000569$$gVol. 5, no. 11, p. e1000569 -$$n11$$pe1000569$$q5:11<e1000569 -$$tPLoS Computational Biology$$v5$$x1553-7358$$y2009
000136030 8564_ $$uhttps://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1000569
000136030 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774268
000136030 8564_ $$uhttps://pub.dzne.de/record/136030/files/DZNE-2020-02352.pdf$$yOpenAccess
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000136030 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000367$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
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000136030 9141_ $$y2009
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