La directionnalité de la délamination collective est régie par l'architecture tissulaire et l'adhésion cellulaire dans le carcinome dépourvu de jonction septés chez la Drosophile
Year: 2024
Type: dissertation
Abstract: Epithelia are tissues made up of polarized cells that rely on apical-basal polarity signals, changes in cell adhesion, and interactions with the cytoskeleton to integrate stimuli and produce coordinated responses to maintain homeostasis. Cell junctions must be robust yet remain plastic to allow collective cell rearrangements without compromising the survival of the organism. In my work I have unveiled a novel, non-occluding function of septate junctions (SJ) in preventing caspase-activation and elimination by cell competitions. I also identified how loss of SJ synergizes with RasV12 to promote apical and basal collective delamination. I characterized the spatiotemporal remodeling of junctional complexes and the cytoskeleton network to decipher the sequence of events required for cells to form tissue folds as well as undergo collective delamination, either apically or basally. Our collaborators developed an in silico model to probe the mechanical properties of the eye disc upon disruption of the remodeling events I identified. Our results, both in silico and in vivo reveal changes in cell adhesion and tissue cytoarchitecture govern the directionality with which tumors delaminate collectively and alive out of an epithelium, a property that is essential to determine the fate of tumors. My work highlights novel, non-occluding functions of SJ in preventing cell extrusion and characterizes how loss of SJ integrity in tumors promotes malignancy. Furthermore, it reveals how tissue architecture and changes in cell adhesion govern the directionality of apical and basal collective delamination, offering new insights into how SJs function to preserve tissue homeostasis and prevent neoplastic transformation.
Source: theses.fr (ABES)
Author: Mira Osuna, Marta
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7048509926
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