Roles of cytoplasmic bridges in cell-cell cohesion and communication

Description du projet

Un examen plus approfondi des connexions cellulaires

Au cours du développement, les cellules se divisent pour produire d’autres cellules. Cela se termine généralement par une abscission, le processus par lequel deux cellules nouvellement nées se séparent complètement. Cependant, certaines cellules restent connectées par des structures appelées ponts cytoplasmiques. Ces ponts peuvent jouer un rôle important dans le maintien des fonctions cellulaires, mais leurs effets demeurent mal compris. Dans ce contexte, le projet CYTO-BRIDGES, financé par le CER, s’intéressera à ces ponts cytoplasmiques en tant qu’organites conservés, essentiels à la fonction cellulaire. Les chercheurs essaieront de comprendre comment ils servent de liens mécaniques et de canaux de communication entre les cellules connectées. En utilisant l’imagerie en direct et des techniques génétiques avancées, le projet étudiera le choanoflagellé simple Salpingoeca rosetta et des cellules souches embryonnaires complexes de souris. Les résultats nous permettront de mieux appréhender la manière dont ces structures influencent les interactions cellulaires dans les organismes multicellulaires.

Objectif

During development, cells divide and make fate decisions. Canonically, cell division ends with the severing of the link between daughter cells in the process called abscission. Yet, across the tree of life, cells can remain connected through cytoplasmic bridges by delaying or inhibiting abscission. Curiously, while bridges are important conserved structures sustaining cellular function, there are little evidence to explain how bridge impact cell function. The aim of the proposal is to investigate the hypothesis that bridges are conserved organelles critical for cell function by providing unique mechanical connexion and an important inter-cellular communication channel. In particular, we will leverage our expertise in live imaging of cell division and biophysics as well as a combination of newly developed genetic and optogenetic manipulations to determine:
1) The role of bridges as a mechanical coupling between connected cells. We will test the contribution of cytoplasmic bridges in creating a physical link between cells and the consequences of disturbing this cohesion for cell function.
2) The role of bridges as an exchange route between connected cells. We will investigate how the regulated exchange of cellular material through bridges impacts cell function.
As bridges can have a simple or a complex structure that could be critical for their function, we will use 2 model systems: the choanoflagellate Salpingoeca rosetta where a structurally simple bridge sustains cell-cell cohesion, and mouse embryonic stem cells where bridges are structurally more complex. While traditional models of bridges are difficult to manipulate, both our models are easy to culture and provide an experimentally tractable system that can shuttle from a unicellular to a multicellular organisation. The comparison between these two model systems will allow us to understand how a fundamental step of cell division could crucially impact the function of cells in a multicellular context.