In Montpellier, France, we are:
ciona embryos viewed by Olivier Tassy
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Transcriptional control of Chordate development and morphogenesis
         Our general aim is to understand how a linear genomic sequence can drive the dynamic formation of a complex 3D multicellular animal, using as a model system the embryos of a close relative of the vertebrates, the ascidian Ciona intestinalis. Ascidians were chosen because of the anatomical and genomic simplicity of these organisms. In addition, this large group of marine animals (>2,300 species) shows an extraordinary conservation of embryonic lineages, cell fates and cell shapes, even between species whose genomes have massively diverged during their 500 MY of parallel evolution. Ascidians thus offer a unique opportunity to decipher the developmental programme of a chordate, and to understand how developmental stability is encoded in genomic DNA.

         Our approach is to move step by step from genome sequence to transcriptional regulation, to the assembly of Gene Regulatory Networks, to their control of cell fates and cell shapes, making full use of the ongoing revolutions in high throughput sequencing and live imaging. We are focusing on two specific developmental programs:
  • the early endoderm, which drives the first major embryonic morphogenetic event, gastrulation.
  • the precursors of dopaminergic neurons, a cell type conserved with vertebrates and with important medical relevance.
         In each of these tissues, we are combining high-throughput sequencing of genomic fragments associated to specific chromatin features (ChIP-seq), comparative genomics between distantly related ascidians species, and computational modelling of cis-regulatory output, to identify large sets of cis-regulatory regions active at successive developmental stages. This cis-regulatory information is computationally integrated with gene expression profiles, and transcription factor DNA-binding specificities into Gene Regulatory Networks (GRNs) active in each cell population. These networks will be mathematically analyzed to characterize their topology and relate it to the evolutionary stability/plasticity of networks among ascidians and with vertebrates. Finally, to link GRNs to morphogenesis, we develop a framework to image and quantitatively simulate the mechanics of the individual and collective cell behaviours that drive gastrulation.

         Our multidisciplinary work is thus at the interface between developmental biology, cell biology, evolutionary biology and systems biology. We hope that the methods and rules established in simple ascidians will pave the way for similar approaches in more complex mammals.
        Our work is supported by national (ANR, CNRS, FRM) and European (FP7 DOPAMINET) funding. Our group is a member of the Laboratory of Excellence (LabEx), EpiGenMed.


Lemaire's Laboratory