Backup mandate Research Council: Embryonic development in ascidians: ERK-signalling based spatial precision and robustness of geometry-controlled cell specification.

Embryonic development is highly organised both in time and space.
It relies on the ability of cells to sense signals from the environment
and activate specific genetic programs. A quantitative understanding of how signaling inputs are integrated to activate lineage-specific gene programs is still lacking. My project aims at developing a mathematical formalism to address this question by focusing on ascidian development. In collaboration with the group of H. Yasuo, we will investigate how, during neural induction at the 32 cells stage, ERK activity is fine-tuned by the geometry of the embryo which determines the fraction of the cell surface in contact with the ligands that activate (FGF) or down-regulate (ephrin) ERK activity. We will next address the molecular mechanism by which a relatively smooth
gradient of ERK activation is transduced into a bimodal expression of the Otx gene, the marker of the neural fate. This work will allow to understand how the ERK pathway communicates signals from cell surface receptors to the DNA in the cell nucleus in a general context. Furthermore, I will quantify the robustness of the signaling-modulated gene regulatory networks (GRN) driving early ascidian development with respect to molecular and geometrical noise. Comparison with other mammalian GRN will allow to identify the structural properties
of these networks responsible for their high sensitivity to the levels of extracellular signaling encoded in the geometry of the embryo.