Comparative analysis of Gene Regulatory Networks in chordate embryos. – Chor-Evo-Net

Gene regulatory networks (GRNs) form the core of the transcriptional programme. The nodes of these networks are the genes for transcription factors and signalling ligands. Their edges are the direct regulatory relationships that link these genes via their cis-regulatory regions. Work in simple organisms such as bacteria and yeast showed that the analysis of the architecture of GRNs provides a powerful way to apprehend how the genetic information encoded in the genome is transformed into a set of operating rules underlying cellular processes, a logic that cannot be analysed through single-gene studies. Extending these analyses to metazoan systems poses a formidable challenge owing to the genomic complexity of these organisms, to the much higher level of sophistication of their transcriptional regulation, and to their multicellular organisation. Looking at embryonic development, when embryos still have a simple anatomical anatomy, is a way to reduce the complexity. The successful partial reconstruction of the developmental GRNs of Drosophila, Urchin, Xenopus and Ascidians was recently reported Although these networks are still very incomplete, their initial analysis has revealed some general structural principles that distinguish metazoan developmental networks from more simple GRNs. Comparative analyses also indicated that changes in the architecture of GRNs constitute a major drive in animal evolution. It has in particular been suggested, but not robustly demonstrated, that specific highly connected regions of GRNs, so called kernels, are highly conserved and may be responsible for the evolutionary stability of phylum-specific traits, such as the body plan. The aim of this application is to reconstruct and mathematically analyse the GRN underlying embryogenesis in the ascidian Ciona intestinalis, which shares with vertebrate a common larval tadpole-like body plan. Further, we will use this reconstructed network as a foundation to analyse, by comparison with teleost fish, the level of evolutionary conservation in the chordate developmental regulatory programme, and its relationship to local connectivity. Through this approach, we hope to identify some of the key conserved mechanisms that led to the emergence of the common ancestor of all chordates.