% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Wittmann:136030,
      author       = {Wittmann, Dominik M and Blöchl, Florian and Trümbach,
                      Dietrich and Wurst, Wolfgang and Prakash, Nilima and Theis,
                      Fabian J},
      title        = {{S}patial analysis of expression patterns predicts genetic
                      interactions at the mid-hindbrain boundary.},
      journal      = {PLoS Computational Biology},
      volume       = {5},
      number       = {11},
      issn         = {1553-7358},
      address      = {San Francisco, Calif.},
      publisher    = {Public Library of Science},
      reportid     = {DZNE-2020-02352},
      pages        = {e1000569},
      year         = {2009},
      abstract     = {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.},
      keywords     = {Algorithms / Animals / Brain: embryology / Brain:
                      metabolism / Brain Mapping: methods / Computational Biology:
                      methods / Diffusion / Fibroblast Growth Factor 8: genetics /
                      Gene Expression Profiling: methods / Gene Expression
                      Regulation, Developmental / Mice / Mice, Inbred C57BL /
                      Models, Biological / Models, Statistical / Transcription,
                      Genetic / Wnt1 Protein: genetics / Fgf8 protein, mouse (NLM
                      Chemicals) / Wnt1 Protein (NLM Chemicals) / Wnt1 protein,
                      mouse (NLM Chemicals) / Fibroblast Growth Factor 8 (NLM
                      Chemicals)},
      cin          = {AG Wurst},
      ddc          = {610},
      cid          = {I:(DE-2719)1140001},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:19936059},
      pmc          = {pmc:PMC2774268},
      doi          = {10.1371/journal.pcbi.1000569},
      url          = {https://pub.dzne.de/record/136030},
}