Boolean Modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord

Anna Lovrics, Yu Gao, Bianka Juhász, István Bock, Helen M. Byrne, András Dinnyés, Krisztián A. Kovács

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Article numbere111430
JournalPloS one
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 14 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Boolean Modelling reveals new regulatory connections between transcription factors orchestrating the development of the ventral spinal cord'. Together they form a unique fingerprint.

  • Cite this