Robustness of the microtubule network self-organization in epithelia

Abstract

Robustness of biological systems is crucial for their survival, however, for many systems its origin is an open question. Here we analyze one sub-cellular level system, the microtubule cytoskeleton. Microtubules self-organize into a network, along which cellular components are delivered to their biologically relevant locations. While the dynamics of individual microtubules is sensitive to the organism's environment and genetics, a similar sensitivity of the overall network would result in pathologies. Our large-scale stochastic simulations show that the self-organization of microtubule networks is robust in a wide parameter range in individual cells. We confirm this robustness in vivo on the tissue-scale using genetic manipulations of Drosophila epithelial cells. Finally, our minimal mathematical model shows that the origin of robustness is the separation of time-scales in microtubule dynamics rates. Altogether, we demonstrate that the tissue-scale self-organization of a microtubule network depends only on cell geometry and the distribution of the microtubule minus-ends.

Deciphering the roles of cell shape and Fat and Dachsous planar polarity in arranging the Drosophila apical microtubule network through quantitative image analysis

“…MTSD correlated with cell elongation ( Figure 5C )—more elongated cells with higher eccentricities had a steeper distribution (smaller MTSD) that reflected more aligned microtubules, with no significant difference between the two regions of the pupal wing examined. Such correlation of the microtubule angle distribution with the cell eccentricity agrees with the reported robustness of microtubule alignment with each other in subapical microtubule networks of epithelial cells ( Płochocka et al. , 2021 ).…”

“…The localization of the minus ends in noncentrosomal networks is of particular interest, as it ensures the correct polarized transport by motor proteins ( Steinhauer and Kalderon, 2006 ; Zhelezov et al. , 2019 ).To examine the possibility that Ft-Ds complexes alter the distribution of the minus ends without affecting the overall organization of subapical microtubules, we turned to the minus-end capping protein Patronin, which localizes at apical junctions and exhibits an asymmetrical distribution in the Drosophila embryonic epidermis that depends on the cell elongation ( Goodwin and Vale, 2010 ; Płochocka et al. , 2021 ).…”

“…, 2016 ). This cell shape–driven microtubule alignment has been shown to be robust in several epithelia, including the Drosophila pupal wing epithelium ( Płochocka et al. , 2021 ).…”

“…, 2021 ). It was further proposed that the degree of microtubule alignment but not the overall direction might be affected by the positioning of microtubule minus ends ( Płochocka et al. , 2021 ).…”

The Bacillus cereus toxin alveolysin disrupts the intestinal epithelial barrier by inducing microtubule disorganization through CFAP100

“…Because microtubule disorganization has been demonstrated to impair the membrane recruitment of cell junction proteins ( 49 , 50 ), we extracted the membrane and cytosolic fractions of Caco-2 monolayer cultures and determined the distribution of cell junction proteins in each fraction. Immunoblot analysis showed that treating the cells with purified Bc-5 alveolysin or with wild-type Bc-5 cells, but not alveolysin mutant Bc-5 cells (Δ4211Δ5613), significantly decreased the membrane accumulation of ZO-1, claudin-4, and E-cadherin (Fig.…”