Understanding the molecular and biophysical mechanisms that drive cell contact re-establishment after division

Cells are generally not found in isolation, but embedded within tissues. Therefore, after every cell division the newly formed cells need to re-establish cell-cell contacts to maintain tissue integrity. The inability to coordinate cell division and cell contact re-establishment can lead to developmental disorders, for example those characterised by a variety of birth defects. Despite its importance in tissue homeostasis, the mechanisms controlling the formation of cell-cell contacts immediately after cell division remain poorly understood.

To identify genes involved in contact re-establishment, we will use our large-scale genetic screen in C. elegans. This screen identified regulators of early embryonic developmental processes, mainly: cell division, cytoskeleton dynamics and membrane composition/organisation. Following this screen, we will design a comprehensive phenotypic analysis to identify genes involved in cytokinesis, which is the process that completes cell division. In collaboration with our partner "Intogral" we will perform quantitative image data analyses upon loss of function of the identified cytokinesis regulators. This will help us determine key biomechanical parameters required for contact re-establishment during cytokinesis. We will use this data to train a computational model to identify early signs of tissue integrity problems. In addition, the molecular characterization of the identified cytokinesis regulators will advance our understanding of the mechanisms that coordinate cell contact re-establishments with other key processes during embryogenesis, for example cell orientation and polarity.