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

PLoS Computational Biology
Dominik M WittmannFabian J Theis

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 a...Continue Reading

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Citations

Feb 27, 2014·Biological cybernetics·Clare E Giacomantonio, Geoffrey J Goodhill
Aug 26, 2014·Database : the Journal of Biological Databases and Curation·Michaela MatthesDietrich Trümbach
May 13, 2010·BMC Bioinformatics·Jan KrumsiekFabian J Theis
Sep 24, 2010·PLoS Computational Biology·Clare E Giacomantonio, Geoffrey J Goodhill
Jan 12, 2013·Cellular and Molecular Life Sciences : CMLS·Sebastian Dworkin, Stephen M Jane
Jun 19, 2013·Orphanet Journal of Rare Diseases·Nadia A AkawiLihadh Al-Gazali
Jul 27, 2010·Journal of Theoretical Biology·Dominik M WittmannFabian J Theis
Jan 5, 2011·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Genevieve Konopka
Aug 29, 2012·Proceedings of the National Academy of Sciences of the United States of America·Isabelle S PeterEric H Davidson

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