Physical models of epithelial morphogenesisRozman, Jan (Avtor) Ziherl, Primož (Mentor) epitheliummorphogenesisvertex modelsurface tensionorganoidsvillifruit flyegg chamberclonal dominanceThe Thesis addresses selected theoretical problems of the mechanics of biological systems that involve epithelial tissues. We first develop a vertex model of epithelial shells that resemble small organoids. We find that collective effects in a system of cell with identical mechanical properties are sufficient for the formation of spherical, stomatocyte, and budded morphologies. However, the formation of branched model organoids also requires a high degree of junctional activity, possibly because it enables a temporary aggregation of topological defects. To elucidate our numerical results, we develop an effective elasticity theory, which allows one to estimate the apico-basal polarity from the tissue-scale modulation of cell height. We then compare these results to morphologies that emerge in a more general model tissue: A strained unsupported epithelial monolayers subject to active junctional noise due to stochastic binding and unbinding of myosin. We find that while uniaxial, biaxial, and isotropic in-plane compressive strains do lead to the formation of longitudinal, herringbone pattern, and labyrinthine folds, respectively, the villi morphology again appears only if junctional tension fluctuations are strong enough to fluidize the tissue. Moreover, the fluidized epithelium features villi even in absence of compressive strain. We also analyze several details of the different epithelial forms including the role of strain rate and the modulation of tissue thickness across folds. Lastly, we use a discrete model that takes into account the topology of linked cells, but not their geometry, to study the emergence of clonal dominance. This phenomenon refers to the situation where the descendants (also known as clones) of one or a few founder cells contribute disproportionally to the cell population of the final tissue. While this is often explained by pre-existing advantages in, e.g., bacterial colonies, it is less understood in development where such biases should not be present. Using clone size data from the fruit fly egg chamber epithelium, we show that clonal dominance can emerge spontaneously due to the coupling of cell divisions.20222022-06-04 08:15:02Doktorsko delo/naloga137169sl