Article (Scientific journals)
Characterization of the proneural gene regulatory network during mouse telencephalon development.
Gohlke, Julia M; Armant, Olivier; Parham, Frederick M et al.
2008In BMC Biology, 6, p. 15
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Keywords :
Algorithms; Animals; Basic Helix-Loop-Helix Transcription Factors/genetics; Bayes Theorem; Cell Adhesion/genetics; Computational Biology; Embryo, Mammalian; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mutation; Nerve Tissue Proteins/genetics; Neurons/cytology; Signal Transduction/genetics; Telencephalon/embryology
Abstract :
[en] BACKGROUND: The proneural proteins Mash1 and Ngn2 are key cell autonomous regulators of neurogenesis in the mammalian central nervous system, yet little is known about the molecular pathways regulated by these transcription factors. RESULTS: Here we identify the downstream effectors of proneural genes in the telencephalon using a genomic approach to analyze the transcriptome of mice that are either lacking or overexpressing proneural genes. Novel targets of Ngn2 and/or Mash1 were identified, such as members of the Notch and Wnt pathways, and proteins involved in adhesion and signal transduction. Next, we searched the non-coding sequence surrounding the predicted proneural downstream effector genes for evolutionarily conserved transcription factor binding sites associated with newly defined consensus binding sites for Ngn2 and Mash1. This allowed us to identify potential novel co-factors and co-regulators for proneural proteins, including Creb, Tcf/Lef, Pou-domain containing transcription factors, Sox9, and Mef2a. Finally, a gene regulatory network was delineated using a novel Bayesian-based algorithm that can incorporate information from diverse datasets. CONCLUSION: Together, these data shed light on the molecular pathways regulated by proneural genes and demonstrate that the integration of experimentation with bioinformatics can guide both hypothesis testing and hypothesis generation.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Gohlke, Julia M
Armant, Olivier
Parham, Frederick M
Smith, Marjolein V
Zimmer, Celine
Castro, Diogo S
Nguyen, Laurent  ;  Université de Liège - ULiège > Département des sciences cliniques > Neurologie
Parker, Joel S
Gradwohl, Gerard
Portier, Christopher J
Guillemot, Francois
Language :
English
Title :
Characterization of the proneural gene regulatory network during mouse telencephalon development.
Publication date :
2008
Journal title :
BMC Biology
eISSN :
1741-7007
Publisher :
BioMed Central, United Kingdom
Volume :
6
Pages :
15
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 28 January 2009

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