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Paul Francois

Publications and source records attributed to Paul Francois.

2 recordsLinked to original sources

Multiscale quantification of tissue behavior during amniote embryo axis elongation

Embryonic axis extension is a complex multi-tissue morphogenetic process responsible for the formation of the posterior part of the amniote body. Cells located in the caudal part of the embryo divide and rearrange to participate in the elongation of the different embryonic tissues (e.g. neural tube, axial and paraxial mesoderm, lateral plate, ectoderm, endoderm). We previously identified the paraxial mesoderm as a crucial player of axis elongation, but how movements and growth are coordinated between the different posterior tissues to drive morphogenesis remain largely unknown. Here we use the quail embryo as a model system to quantify cell behavior and movements in the various tissues of the elongating embryo. We first quantify the tissue-specific contribution to axis elongation by using 3D volumetric techniques, then quantify tissue-specific parameters such as cell density and proliferation at different embryonic stages. To be able to study cell behavior at a multi-tissue scale we used high-resolution 4D imaging of transgenic quail embryos expressing constitutively expressed fluorescent proteins. We developed specific tracking and image analysis techniques to analyze cell motion and compute tissue deformations in 4D. This analysis reveals extensive sliding between tissues during axis extension. Further quantification of \"tissue tectonics\" showed patterns of rotations, contractions and expansions, which are coherent with the multi-tissue behavior observed previously. Our results confirm the central role of the PSM in axis extension; we propose that the PSM specific cell proliferation and migration programs control the coordination of elongation between tissues during axis extension.

Developmental Biology

Phenotypic spandrel: absolute discrimination and ligand antagonism

We consider the general problem of absolute discrimination between categories of ligands irrespective of their concentration. An instance of this problem is immune discrimination between self and not-self. We connect this problem to biochemical adaptation, and establish that ligand antagonism - the ability of sub threshold ligands to negatively impact response - is a necessary consequence of absolute discrimination.Thus antagonism constitutes a \"phenotypic spandrel\": a phenotype existing as a necessary by-product of another phenotype. We exhibit a simple analytic model of absolute discrimination displaying ligand antagonism, where antagonism strength is linear in distance from threshold. This contrasts with proofreading based models, where antagonism vanishes far from threshold and thus displays an inverted hierarchy of antagonism compared to simple model. The phenotypic spandrel studied here is expected to structure many decision pathways such as immune detection mediated by TCRs and FceRIs.

Systems Biology