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Palacios, I. I.

Publications and source records attributed to Palacios, I. I..

3 recordsLinked to original sources

Mechanical context defines integrin requirement for maintaining epithelia architecture

Epithelial tissues form cohesive sheets of cells anchored to an underlying basement membrane (BM). They are broadly classified as simple or stratified, each fulfilling distinct physiological roles. While mechanisms driving stratification are increasingly well characterized, those safeguarding simple epithelial architecture remain poorly defined. Here, we address this knowledge gap using the simple follicular epithelium of Drosophila as a model. Combining live imaging, quantitative image analysis, manipulation of BM mechanical properties and biophysical measurements, we uncover previously unrecognized integrin-dependent mechanisms esential for preserving simple epithelial integrity. In addition to their known role in orienting cell division, integrins regulate cell reintegration dynamics and modulate surface tension at the cellular level. We further demonstrate that the maintenance of epithelial architecture is governed by mechanisms acting across both cellular and tissue scales. In our model, BM mechanical properties--including stiffness anisotropy--cooperate with integrin-mediated adhesion and tissue geometry to preserve epithelial organization. Given the central role of epithelial disorganization in tumorigenesis, elucidating these mechanical and molecular regulators is critical for understanding epithelial morphogenesis, maintaining tissue homeostasis, and uncovering the early events of cancer progression.

cell biology↗

Artificial Cells Evidence Apical Compressive Forces Building up During Neuroepithelial Organoid Early Development

During early stages of development of cerebral organoids, budding neuroepithelia display striking changes in size and morphology, occurring very rapidly. Whilst mechanical forces mediated by cadherin-cadherin junctions are known to control the assembly, maturation and stability of epithelia, little is known of the mechanical context associated with neuroepithelial organoid development. In this report, we demonstrate a rapid translocation of YAP to budding neuroepithelial apical junctions, suggesting the build-up of strong compressive forces early on in their development. To study the mechanics of budding rosettes, we designed oil microdroplets stabilised by protein nanosheets displaying cadherin receptors, able to engage with receptors presented by neighbouring neuroepithelial cells, to integrate into embryoid bodies and developing organoids. The resulting artificial cells are able to sustain the formation of mature junctions with neighbouring cells and lead to the recruitment of tight junction maturation proteins such as ZO1. During early budding of neuroepithelial rosettes, artificial cells are found to be rapidly expelled from the developing organoids, further evidencing apical compressive forces. These forces are not opposed by sufficiently strong shear forces from neighbouring cells, or adhesive forces maintaining anchorage to the apical junction, to induce deformation of artificial cells.

bioengineering↗

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↗