Santa-Cruz Mateos, C. | bioRxiv Science

bioRxiv2025

Direct observation of Notch signalling induced transcription hubs mediating gene-expression responses

Developmental decisions rely on cells making accurate transcriptional responses to signals they receive, as with Notch pathway activity. Local condensates or transcription factor hubs are a proposed mechanism for facilitating gene activation by nuclear complexes. To investigate their importance in endogenous Notch signalling, we deployed multi-colour live-imaging to measure Notch transcription-complex enrichment at a target gene locus in combination with the transcription dynamics. The co-activator Mastermind (Mam) was present in signalling-dependent nuclear foci, during Notch active developmental stages. Tracking these highly-dynamic Mam hubs together with transcription in the same nucleus, revealed that their condensation precedes and correlates with the profile of transcription and becomes stabilized if transcription is inhibited. Manipulations to signalling levels had concordant effects on hub intensities and transcription profiles, altering their probability and amplitude. Together the results argue that signalling induces the formation of transcription hubs whose properties are instrumental in the quantitative gene expression response to Notch activation.

developmental biology↗

bioRxiv2019

Integrins control tissue morphogenesis and homeostasis by sustaining the different types of intracellular actin networks

Forces generated by the actomyosin cytoskeleton are key contributors to the generation of tissue shape. Within the cell, the actomyosin cytoskeleton organizes in different types of networks, each of them performing distinct roles. In addition, although they normally localize to precise regions of the cells, they are rarely independent and often their dynamics influence each other. In fact, the reorganization of a given structure can promote the formation of another, conversions that govern many morphogenetic processes. In addition, maintenance of a specific actomyosin network organization in a differentiated tissue might be equally important. Failure to do so could lead to undesired cell state transitions, which in turn would have drastic consequences on the homeostasis of the tissue. Still, little is known about the mechanisms that ensure controlled transitions between actomyosin networks during morphogenesis or their maintenance in a differentiated tissue. Here, we use the Drosophila follicular epithelium to show that cell-ECM interactions mediated by integrins are necessary for the establishment and maintenance of the different actomyosin networks present in these epithelial cells. Elimination of integrins in a group of follicle cells results in changes in the F-actin levels and physical properties of their intracellular actomyosin networks. Integrin mutant follicle cells have reduced number of basal stress fibers. They also show increased cortical F-actin levels and tension, which interferes with proper basal surface growth. Finally, clonal elimination of integrins also triggers non-autonomous behavioural changes in neighbouring wild types cells, which now reorganize their actin cytoskeleton and spread and overlay the mutant ones. Based on these results, we propose that cell-ECM interactions mediated by integrins regulate epithelia morphogenesis and homesostasis by preserving the different types of intracellular actin networks.

cell biology↗