Séminaire MMC : Role of mechanical tensile forces in cell fate acquisition

DATE : Vendredi 20 Janvier 2017, 11h
               Salle 120, Bat.11E

Intervenants : Mathieu Pinot, Marion Daudé, Karen Bellec, Roland Le Borgne
Institute of Genetics and Development of Rennes, CNRS UMR 6290, team ‘Epithelia Dynamics and Mechanics- polarity, division and fate acquisition’.

During the development, epithelial tissues must grow or regenerate to maintain their integrity. This is achieved thanks to epithelial cell division that lead to a new interface between daughter cells. The formation of these new interfaces is controlled by tension forces generated by the intracellular acto-myosin network and transmitted by adherens junctions composed of E-Cadherin. Moreover, epithelia are mosaics tissues composed cells of distinct identities exhibiting different bio-mechanical properties and fulfilling the functions of a given epithelium. However, the interplay between mechanical tensile forces and acquisition of cellular identity remains unknown.
We used dorsal thorax of Drosophila pupae that consists in a single-layered neuroepithelium that produces epidermal cells that divide symmetrically and sensory organ precursor cells that divide asymmetrically to generate an anterior pIIb and a posterior pIIa daughter cell. The acquisition of cell identity is controlled through the differential activation of Notch by the ligand Delta present on the surface of adjacent cells. It has been proposed that the sorting of Notch receptor and ligand Delta along the apical-basal axis of epithelial cells during cytokinesis is a mechanism for controlling the activation of the pathway. In particular our previous studies led to the proposal that Delta/Notch interaction is localized at the level of adherens junctions where mechanical tensile forces occur.
To investigate the interplay between Notch activation pathway and mechanical forces, we used laser nano-dissection to ablate new formed adherens junctions and we measured the resulting relaxation of the network to evaluate the local ‘tension’ properties. We observed a progressive acquisition of tensile forces during cytokinesis, corresponding to a switch from a ‘low’ to a ‘high’ tense interface. Measurements performed on junction resulting of symmetric division present a ‘high-tense’ behaviour whereas pIIa/pIIb interface resulting of asymmetric division present a ‘low-tense’ behaviour. We are focusing on the role of regulators of membrane traffic, cell polarity, acto-myosin contractility, to isolate the molecular mechanisms and associated mechanical properties related to Notch activation pathway. Our study aims to investigate the interplay between mechanical properties of interfaces and acquisition of cellular identity.

 

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