Dr. Olivier Cinquin

Olivier’s work was focused on the acquisition of a spatial structure during embryo development, which involves the differentiation of cells, often according to positional information. He suggested that the complexity of the molecular networks regulating differentiation and of the mechanisms generating positional information makes it necessary to study them by means of mathematical modeling. Vertebrate embryos also acquire a segmented structure during somitogenesis; this requires spatial and temporal variations in gene expression, which mathematical modeling can also help understand.

He proposed a molecular mechanism for the somitogenesis clock, which accounts for intercellular synchronisation, and is based on positive feedback, even though it is compatible with all experimental data interpreted as showing that the clock is based on negative feedback. He also proposed experiments to test this model, involving real-time clock reporters, as well as inducible systems to induce spatially-controlled perturbations.

Because theoretical and experimental results had led to conflicting ideas as to how useful positional information could be established, he pointed out that some models of extracellular diffusion of morphogen exhibit inadequate traveling waves of receptor saturation. Oliver proposed two alternative (but not mutually exclusive) models, which are based on recent experimental results highlighting the roles of extracellular glycoproteins and morphogen oligomerization.

The readout of positional information is translated to a discrete set of gene expression patterns, but it has been also observed in numerous contexts that genes regulating differentiation are initially co-expressed in progenitors despite their antagonism. Olivier characterised conditions under which three classes of generic ”master regulatory networks” can behave as a ”multi-switch”, directing differentiation in an all-or-none fashion to a specific cell-type chosen among more than two possible outcomes. Because bHLH dimerisation networks can readily display coexistence of many antagonistic factors when competition is low, he finally proposed that decision-making could be forced by a transient increase in competition. This could in turn correspond to some unexplained experimental observations related to Id proteins.

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