Biology subjects

Erdemci-Tandogan, G.

Publications and source records attributed to Erdemci-Tandogan, G..

8 recordsLinked to original sources

bioRxiv2026

Cell intrinsic dynamics guide neuroblast ingression independent of tissue fluidity

Morphogenesis involves the coordination of multiple cellular processes that occur simultaneously within developing tissues. During early Drosophila embryogenesis, neuroblast (NB) ingression occurs concurrently with germ band extension (GBE), yet whether these processes interact mechanistically remains unclear. Here, we combine mathematical modelling with quantitative live imaging to investigate whether tissue-level mechanics during GBE influence NB ingression dynamics. Mathematical modelling predicted that reducing tissue fluidity through impaired cellular rearrangements should slow NB ingression by increasing mechanical resistance. Experimental analysis of mutants in which cell intercalation and GBE are disrupted revealed a dramatic reduction in tissue fluidity. However, NB ingression rates remained largely unaffected when tissue fluidity decreased. Incorporating cell-intrinsic myosin anisotropy and endocytosis-contractility coupling into our mathematical model rescued the rate of neuroblast ingression in solid-like tissues. Thus, our findings suggest that cell-intrinsic mechanisms, rather than tissue-level fluidity, maintain ingression kinetics. More broadly, these results illustrate how developmental systems can achieve robustness by insulating critical cellular events from tissue-level mechanical variability. Statement of SignificanceMorphogenesis requires coordination of cellular processes in tissues undergoing mechanical transitions. While recent work highlights the importance of tissue fluidity in morphogenesis, whether tissue-level mechanical changes influence concurrent cellular events remains unclear. Combining mathematical modelling with quantitative live imaging, we tested whether tissue fluidization during Drosophila germ-band extension regulates neuroblast ingression. Shape-based vertex models failed to predict tissue mechanical states when myosin was disrupted. Instead, incorporating cellular rearrangement delays recapitulated phenotypes independent of cell shape. Strikingly, we showed that neuroblast ingression remains robust despite tissue solidification in vivo. Biophysical modelling suggests that coupled cell contractility and endocytosis maintains robust ingression despite tissue solidification. Our work shows that developmental programs can be mechanically insulated from tissue-scale changes, thus enabling developmental robustness.

developmental biology↗

bioRxiv2026

E-cadherin clustering as a regulator of morphogenesis

Cell adhesion enables animal multicellular development. E-cadherin and the cadherin-catenin adhesion complex at adherens junctions are engaged in dynamic interactions with actomyosin generated contractile forces to drive epithelial morphogenesis. However, our understanding of how adhesion is regulated and how the tuning of adhesion contributes to morphogenesis remains incomplete. One key determinant of E-cadherin adhesion strength is clustering of the cadherin-catenin adhesion complex, a property studied extensively in vitro. Here, we use optogenetics to enhance E-cadherin cluster formation in the Drosophila embryo. Enlarged clusters were associated with increased E-cadherin surface abundance, assembled a normal cadherin-catenin complex, and showed reduced membrane mobility and turnover consistent with an increase in cell adhesion strength. Drosophila embryos with enhanced E-cadherin clustering displayed a severe reduction in cell intercalation and convergent extension of the anterior-posterior axis. To account for these observations, we modified existing vertex models to include junction-specific viscous forces representing E-cadherin-mediated friction between cells. This dissipative adhesion model predicts that enhanced adhesion increases resistance to cell rearrangements, thereby reducing cell neighbor exchanges and impairing convergent extension. To test model predictions, we analyzed two types of morphogenetic movements in embryos with enhanced E-cadherin clustering. Neuroblast ingression, which requires both apical constriction and cell rearrangement, was severely slowed. In contrast, mesoderm invagination, which requires apical constriction without neighbor exchanges, proceeded normally. Our findings suggest that optogenetic clustering, in contrast to overexpression of E-cadherin, is a valuable tool to examine the consequences of enhancing adhesion strength in tissue morphogenesis. Moreover, we propose that regulating E-cadherin clustering is essential for movements that require cell-cell contact changes.

cell biology↗

bioRxiv2025

Cell divisions both challenge and refine tissue boundaries in the Drosophila embryo

Tissue boundaries pattern embryos, suppress tumours, and provide directional cues. Tissue boundaries are associated with supracellular cables formed by actin and the molecular motor non-muscle myosin II. Actomyosin cables generate tension that prevents cell mixing. Whether other cellular behaviours contribute to the formation of linear interfaces between cell populations remains unclear. In the Drosophila embryo, an actomyosin-based boundary separates the ectoderm from the mesectoderm, a group of neuronal and glial progenitors. Mathematical modelling predicted that cell divisions in the ectoderm challenge the mesectoderm-ectoderm (ME) boundary. Consistent with this, suppressing ectoderm cell divisions in vivo prevented cell mixing across the ME boundary when actomyosin-based tension was lost. Our mathematical model also predicted that cell divisions sharpen the ME boundary by reducing tension and increasing cell motility in the ectoderm. We found that inhibiting ectoderm divisions in vivo reduced boundary linearity. Using laser ablation and cell tracking, we demonstrated that cell divisions reduced junctional tension and increased cell movement in the ectoderm. Together, our results reveal that cell divisions facilitate cellular rearrangements to increase fluidity in a novel mechanism for boundary refinement.

developmental biology↗

bioRxiv2022

Myosin waves and a mechanical asymmetry guide the oscillatory migration of Drosophila cardiac progenitors

Heart development begins with the formation of a tube, as cardiac progenitors migrate from opposite sides of the embryo and meet medially. Defective cardiac progenitor movements cause congenital heart defects. However, the mechanisms of cell migration during early heart development remain poorly understood. We investigated the mechanisms of movement of the Drosophila cardiac progenitors, the cardioblasts. Using quantitative time-lapse microscopy, we found that cardioblasts did not advance monotonically. Instead, cardioblasts took periodic forward and backward steps as they migrated. The forward steps were greater in both amplitude and duration, resulting in net forward movement of the cells. The molecular motor non-muscle myosin II displayed an alternating pattern of localization between the leading and trailing ends of migrating cardioblasts, forming oscillatory waves that traversed the cells. The alternating pattern of myosin polarity was associated with the alternative contraction and relaxation of the leading and trailing edges of the cell. Mathematical modelling predicted that forward migration requires the presence of a stiff boundary at the trailing edge of the cardioblasts. Consistent with this, we found a supracellular actin cable at the trailing edge of the cardioblasts. When we reduced the tension sustained by the actin cable, the amplitude of the backward steps of cardioblasts increased, thus reducing the net forward speed of migration. Together, our results indicate that periodic cell shape changes coupled with a polarized actin cable produce asymmetrical forces that guide cardioblast migration.

developmental biology↗

bioRxiv2021

3D viscoelastic drag forces drive changes to cell shapes during organogenesis in the zebrafish embryo

The left-right organizer in zebrafish embryos, Kupffers Vesicle (KV), is a simple organ that undergoes programmed asymmetric cell shape changes that are necessary to establish the left-right axis of the embryo. We use simulations and experiments to investigate whether 3D mechanical drag forces generated by the posteriorly-directed motion of the KV through the tailbud tissue are sufficient to drive such shape changes. We develop a fully 3D vertex-like (Voronoi) model for the tissue architecture, and demonstrate that the tissue can generate drag forces and drive cell shape changes. Furthermore, we find that tailbud tissue presents a shear-thinning, viscoelastic behavior consistent with those observed in published experiments. We then perform live imaging experiments and particle image velocimetry analysis to quantify the precise tissue velocity gradients around KV as a function of developmental time. We observe robust velocity gradients around the KV, indicating that mechanical drag forces must be exerted on the KV by the tailbud tissue. We demonstrate that experimentally observed velocity fields are consistent with the viscoelastic response seen in simulations. This work also suggests that 3D viscoelastic drag forces could be a generic mechanism for cell shape change in other biological processes. HighlightsO_LInew physics-based simulation method allows study of dynamic tissue structures in 3D C_LIO_LImovement of an organ through tissue generates viscoelastic drag forces on the organ C_LIO_LIthese drag forces can generate precisely the cell shape changes seen in experiment C_LIO_LIPIV analysis of experimental data matches simulations and probes tissue mechanics C_LI Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

developmental biology↗

bioRxiv2021

Effect of cellular rearrangement time delays on the rheology of vertex models for confluent tissues

Large-scale tissue deformation during biological processes such as morphogenesis requires cellular rearrangements. The simplest rearrangement in confluent cellular monolayers involves neighbor exchanges among four cells, called a T1 transition, in analogy to foams. But unlike foams, cells must execute a sequence of molecular processes, such as endocytosis of adhesion molecules, to complete a T1 transition. Such processes could take a long time compared to other timescales in the tissue. In this work, we incorporate this idea by augmenting vertex models to require a fixed, finite time for T1 transitions, which we call the "T1 delay time". We study how variations in T1 delay time affect tissue mechanics, by quantifying the relaxation time of tissues in the presence of T1 delays and comparing that to the cell-shape based timescale that characterizes fluidity in the absence of any T1 delays. We show that the molecular-scale T1 delay timescale dominates over the cell shape-scale collective response timescale when the T1 delay time is the larger of the two. We extend this analysis to tissues that become anisotropic under convergent extension, finding similar results. Moreover, we find that increasing the T1 delay time increases the percentage of higher-fold coordinated vertices and rosettes, and decreases the overall number of successful T1s, contributing to a more elastic-like - and less fluid-like - tissue response. Our work suggests that molecular mechanisms that act as a brake on T1 transitions could stiffen global tissue mechanics and enhance rosette formation during morphogenesis.

biophysics↗

bioRxiv2019

Anisotropy links cell shapes to a solid-to-fluid transition during convergent extension

Within developing embryos, tissues flow and reorganize dramatically on timescales as short as minutes. This includes epithelial tissues, which often narrow and elongate in convergent extension movements due to anisotropies in external forces or in internal cell-generated forces. However, the mechanisms that allow or prevent tissue reorganization, especially in the presence of strongly anisotropic forces, remain unclear. We study this question in the converging and extending Drosophila germband epithelium, which displays planar polarized myosin II and experiences anisotropic forces from neighboring tissues, and we show that in contrast to isotropic tissues, cell shape alone is not sufficient to predict the onset of rapid cell rearrangement. From theoretical considerations and vertex model simulations, we predict that in anisotropic tissues two experimentally accessible metrics of cell patterns--the cell shape index and a cell alignment index--are required to determine whether an anisotropic tissue is in a solid-like or fluid-like state. We show that changes in cell shape and alignment over time in the Drosophila germband indicate a solid-to-fluid transition that corresponds to the onset of cell rearrangement and convergent extension in wild-type embryos and are also consistent with more solid-like behavior in bnt mutant embryos. Thus, the onset of cell rearrangement in the germband can be predicted by a combination of cell shape and alignment. These findings suggest that convergent extension is associated with a transition to more fluid-like tissue behavior, which may help accommodate tissue shape changes during rapid developmental events.

developmental biology↗

bioRxiv2018

Tissue flow induces cell shape changes during organogenesis

In embryonic development, cell shape changes are essential for building functional organs, but in many cases the mechanisms that precisely regulate these changes remain unknown. We propose that fluid-like drag forces generated by the motion of an organ through surrounding tissue could generate changes to its structure that are important for its function. To test this hypothesis, we study the zebrafish left-right organizer, Kupffers vesicle (KV), using experiments and mathematical modeling. During development, monociliated cells that comprise the KV undergo region-specific shape changes along the anterior-posterior axis that are critical for KV function: anterior cells become long and thin, while posterior cells become short and squat. Here, we develop a mathematical vertex-like model for cell shapes, which incorporates both tissue rheology and cell motility, and constrain the model parameters using previously published rheological data for the zebrafish tailbud [Serwane et al.] as well as our own measurements of the KV speed. We find that drag forces due to dynamics of cells surrounding the KV could be sufficient to drive KV cell shape changes during KV development. More broadly, these results suggest that cell shape changes could be driven by dynamic forces not typically considered in models or experiments.

biophysics↗