Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord Journal Article


Author(s): Lovrics, Anna; Gao, Yu; Juhász, Bianka; Bock, István; Byrne, Helen M; Dinnyés, András; Kovács, Krisztián
Article Title: Boolean modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord
Affiliation IST Austria
Abstract: We have assembled a network of cell-fate determining transcription factors that play a key role in the specification of the ventral neuronal subtypes of the spinal cord on the basis of published transcriptional interactions. Asynchronous Boolean modelling of the network was used to compare simulation results with reported experimental observations. Such comparison highlighted the need to include additional regulatory connections in order to obtain the fixed point attractors of the model associated with the five known progenitor cell types located in the ventral spinal cord. The revised gene regulatory network reproduced previously observed cell state switches between progenitor cells observed in knock-out animal models or in experiments where the transcription factors were overexpressed. Furthermore the network predicted the inhibition of Irx3 by Nkx2.2 and this prediction was tested experimentally. Our results provide evidence for the existence of an as yet undescribed inhibitory connection which could potentially have significance beyond the ventral spinal cord. The work presented in this paper demonstrates the strength of Boolean modelling for identifying gene regulatory networks.
Journal Title: PLoS One
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2014-11-14
Start Page: Article number: e111430
Copyright Statement: CC BY 4.0
URL:
DOI: 10.1371/journal.pone.0111430
Notes: This publication was based on work supported in part by IDPbyNMR, PluriSys, InduStem, RESOLVE, EpiHealth, Stem-Cam, ANISTEM (grant agreement numbers PITN-GA-2010-264257, HEALTH-F4-2009-223485, PIAP-GA-2008-230675, FP7-HEALTH-F4-2008-202047, HEALTH-2012-F2-278418, PIAP-GA-2009-251186, PIAPP-GA-2011-286264) projects funded by the EC Seventh Framework Programme, Research Centre of Excellence, 8526-5/2014/TUDPOL, Award No. KUK-C1-013-04, made by King Abdullah University of Science and Technology (KAUST) and the IST FELLOWSHIP awarded to Krisztián A Kovács (Project: P IST EU01 under REA grant agreement n ° 291734). Al, YG, BJ and KK were affiliated to Biotalentum Ltd. IB and AD are still affiliated to Biotalentum Ltd, and received salary from them to support this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Open access: yes (OA journal)