Periodic Reporting for period 3 - EPAF (Role of Epithelial Apoptotic Force in Morphogenesis)
Reporting period: 2018-09-01 to 2020-02-29
We know that mechanics is playing an important role in tissue dynamics both in physiological and pathological contexts and believe that this work will be of interest to a wide scientific community.
In a first part of the project, we are trying to identify what are the key players at the cellular level responsible for force generation. We recently identified a cellular mechanism responsible for force generation which involves the creation of a contractile structure of acto-myosin attached to a basally anchored nucleus, creating a basal resistance point to the force.
In the second part of the project, we tested if other cells than the dying ones could induce force during their extrusion. We discover that other type of delaminating cell could also actively influence their environment suggesting that epithelial cell extrusion could have a general impact in tissue tension and shape.
Comparing different morphogenetic events, we revealed a striking similarity between dying cells and cell becoming mesenchymal and migratory at the time they are preparing to leave the epithelium. Both are pulling on the tissue and participate to its remodeling.
These works also support the idea that folding processes required not only apical constriction but also another set of forces generated perpendicular to the plane of the epithelium.
Altogether, this work open new avenues in the field of mechano-biology and will be of interest to an expanding community.
For the second part of this project, we plan to decipher how these force are transmitted to the tissue and what are the conditions allowing a long range or short range transmission of forces generated locally at the level of a few delaminating cells. We also want to address how a similar mechanism of force generation can be generated in processes having a very different outcome such as apoptosis and epithelial-mesenchymal transition.