Etemadi, E. | Search bioRxiv

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↗