Marco Meer

Last Name

Meer

First Name

Marco

ORCID

0000-0003-4501-6121

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Publications 1 - 5 of 5

Minimisation of surface energy drives apical epithelial organisation and gives rise to Lewis’ law
Meer, Marco; Iannini, Antonella; Villa-Fombuena, Gema; et al. (2019)
bioRxiv
The packing of cells in epithelia exhibits striking regularities, regardless of the organism and organ. One of these regularities is expressed in Lewis’ law, which states that the average apical cell area is linearly related to the number of neighbours, such that cells with larger apical area have on average more neighbours. The driving forces behind the almost 100-year old Lewis’ law have remained elusive. We now provide evidence that the observed apical epithelial packing minimizes surface energy at the intercellular apical adhesion belt. Lewis’ law emerges because the apical cell surfaces then assume the most regular polygonal shapes within a contiguous lattice, thus minimising the average perimeter per cell, and thereby surface energy. We predict that the linear Lewis’ law generalizes to a quadratic law if the variability in apical areas is increased beyond what is normally found in epithelia. We confirm this prediction experimentally by generating heterogeneity in cell growth in Drosophila epithelia. Our discovery provides a link between epithelial organisation, cell division and growth and has implications for the general understanding of epithelial dynamics.
Cell-based simulations of biased epithelial lung growth
Stopka, Anna; Meer, Marco; Iber, Dagmar (2019)
Physical Biology
During morphogenesis, epithelial tubes elongate. in the case of the mammalian lung, biased elongation has been linked to a bias in cell shape and cell division, but it has remained unclear whether a bias in cell shape along the axis of outgrowth is sufficient for biased outgrowth and how it arises. Here, we use our 2D cell-based tissue simulation software $\mathtt{ LBIBCell }$ to investigate the conditions for biased epithelial outgrowth. We show that the observed bias in cell shape and cell division can result in the observed bias in outgrowth only in the case of strong cortical tension, and comparison to biological data suggests that the cortical tension in epithelia is likely sufficient. We explore mechanisms that may result in the observed bias in cell division and cell shapes. To this end, we test the possibility that the surrounding tissue or extracellular matrix acts as a mechanical constraint that biases growth in the longitudinal direction. While external compressive forces can result in the observed bias in outgrowth, we find that they do not result in the observed bias in cell shapes. We conclude that other mechanisms must exist that generate the bias in lung epithelial outgrowth.
Aboave-Weaire’s law in epithelia results from an angle constraint in contiguous polygonal lattices
Vetter, Roman; Meer, Marco; Gómez, Harold; et al. (2019)
bioRxiv
It has long been noted that the cell arrangements in epithelia, regardless of their origin, exhibit some striking regularities: first, the average number of cell neighbours at the apical side is (close to) six. Second, the average apical cell area is linearly related to the number of neighbours, such that cells with larger apical area have on average more neighbours, a relation termed Lewis’ law. Third, Aboav-Weaire’s (AW) law relates the number of neighbours that a cell has to that of its direct neighbours. While the first rule can be explained with topological constraints in contiguous polygonal lattices, and the second rule (Lewis’ law) with the minimisation of the lateral contact surface energy, the driving forces behind the AW law have remained elusive. We now show that also the AW law emerges to minimise the lateral contact surface energy in polygonal lattices by driving cells to the most regular polygonal shape, but while Lewis’ law regulates the side lengths, the AW law controls the angles. We conclude that global apical epithelial organization is the result of energy minimisation under topological constraints.
FGF8 induces chemokinesis and regulates condensation of mouse nephron progenitor cells
Sharma, Abhishek; Meer, Marco; Dapkunas, Arvydas; et al. (2022)
Development
Kidneys develop via iterative branching of the ureteric epithelial tree and subsequent nephrogenesis at the branch points. Nephrons form in the cap mesenchyme as the metanephric mesenchyme (MM) condenses around the epithelial ureteric buds (UBs). Previous work demonstrated that FGF8 is important for the survival of nephron progenitor cells (NPCs), and early deletion of Fgf8 leads to the cessation of nephron formation, which results in post-natal lethality. We now reveal a novel function of FGF8. By combining transgenic mouse models, quantitative imaging assays, and data-driven computational modelling, we show that FGF8 has a strong chemokinetic effect and that this chemokinetic effect is important for the condensation of NPCs to the UB. The computational model shows that the motility must be lower close to the UB to achieve NPC attachment. We conclude that the FGF8 signalling pathway is crucial for the coordination of NPC behaviour to condensate at the UB. Chemokinetic effects have also been described for other FGFs and may be generally important for the formation of mesenchymal condensates.
Cell-Based Simulations of Tissue Patterning During Morphogenesis
Meer, Marco (2022)
Spatial tissue patterning during early morphogenesis depends on the coordinated movement and shape change of tissue cells. Therefore, the identification of the driving forces requires both the quantification of cellular features from image data and computational modelling of tissue dynamics at cellular resolution. Although significant progress has been made in both areas, there are still many unanswered questions. In this work, a mechanochemical simulation framework is applied to model the dynamics of both confluent and non-confluent tissues. First, we review the theory of the topology of epithelial network configurations. Subsequently, we model the self-organization of mesenchymal cells in the nephrogenic niche. Finally, we examine individual aspects of confluent tissue cell mechanics. The following is a brief outline of these investigations. In the first part of this thesis, we investigate how linear relationships between the size and shape of apical cell surfaces arise in epithelia by comparing data and computer modelling with previous explanations. Our results show that, in addition to the known effects of tension and adhesion on cell shape, the size variability of apical cell surfaces is a crucial parameter. Furthermore, our simulations predict that if the size variability of apical cell surfaces is greater than that of most epithelia, this will lead to a nonlinear relationship between size and shape of apical cell surfaces. In the second part of this work, we investigate how mesenchymal cells condense to the adjacent epithelium while swarming through the nephrogenic niche. Although cells are known to switch between adhesive and motile states to coordinate collective processes such as migration or tissue remodelling, it is not yet known how mesenchymal condensation is regulated. Experimental quantifications of mesenchymal cell behaviour and cellular properties reveal a chemokinetic effect of the autocrine factor FGF8, and a computational model of reciprocal signalling between mesenchymal and epithelial cells reproduces the experimentally observed motility gradient and mesenchymal condensation. Moreover, the simulations predict that the balance between mesenchymal and epithelial signalling must be precisely regulated for mesenchymal condensation to occur. The last part of this thesis covers the effect of cell mechanical properties on intercellular contact-dependent signalling and differentiation as well as tissue outgrowth in the primordia of the mouse.

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Marco Meer

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