- Epithelial Tissue Morphogenesis Assessed by Divided Media hal link

Auteur(s): Cañadas P., Chélin Y., Averseng J., Maurin B.

Conférence invité: Seventh World Congress of Biomechanics WCB2014 (Boston, US, 2014-07-11)

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Tissue morphogenesis is a key point remaining weakly understood in development biology. Indeed, most of plants or animals epithelial tissues show analogous cell polygonal distributions.Accordingly, one may think of invariant features governing this process.We propose an original 2D-model based on divided media to explore the potential role of mechanics in epithelial morphogenesis. A cell is represented by repulsive “cytoplasm-grains”maintained inside a closed membrane composed of “membrane-gains” connected via “membrane-tendons”. We consider different substrate geometries: a sphere, to mimick Ciona Intestinaliseggs and a plane, as for culture boxes. The evolution through time is simulated using the molecular dynamics approach where cell growth, division and apoptosis are computed to simulatethe formation of tissues following two mechanisms: (i) accretion and (ii) proliferation.In the accretion scenario, the sphere and the cells grow while new small cells are inserted randomly. Thus, the growth parameters are related to the arrival of new cells and the size of thecells and of the spherical egg.In the proliferative scenario, the tissue takes form by growing of cells and afterwards dividing into child cells, and/or dying (apoptosis). It is governed by the ratio between the number ofapoptosis and of mitoses, defined as the “proliferation rate”.The numerical results obtained following the two scenarii reproduce the experimental observations. This indicates that mechanical interactions could play a major role in tissue formation. Atthe opposite, both the substrate geometry and boundary conditions do not significantly influence cell geometry, what was hardly foreseeable.In the accretion scenario, the number of hexagonal cells and the standard deviations for the polygonal distributions decrease slightly as the tissue formation rate decreases: a slowerdevelopment speed could allow the cells to pack better during their reorganization and growth, resulting in a more reproductible topology. Otherwise, the number of hexagonal cells obtainedfor each accretion scenario is always higher than with the proliferative one, which may be attributed to the disruptive role of cell division in tissue reorganization.In the proliferation scenario, the numerical distributions get closer to experimental observations when the proliferation rate increases. In parallel, the corresponding standard deviationsdecrease. Accordingly, apoptosis may play a crucial role in tissue morphogenesis regulation by counterbalancing the plausible disruptive effect of cell division.In spite of its oversimplification, this promising approach based on an original cell-tissue modelling may allow new useful architectural descriptions and mechanical analysis in epithelialmorphogenesis.

Commentaires: Invitation to a keynote lecture (by Taiji Adachi and Dimitrije Stamenovic) for the session "Computational modeling of cellular and cytoskeletal mechanics"