Epithelial monolayer morphogenesis

Epithelia act as a physical barrier against external aggressions but also ensure organ functionality. If not correctly assembled or dysfunctional, this leads to pathological situations that include a variety of diseases spanning from rare developmental syndromes or cancer.

How epithelia coordinate and harmonize the responses of each cell with not only their nearest neighbors, but entire tissue, to guarantee proper spatial arrangement, integrity and functionality is still not well understood. So far, the question of epithelial coherence has been mainly tackled in invertebrate models during development or in transformed cell lines in culture.

The intestinal epithelium is a tremendous model for this field of research, as it is one of the most fast-proliferative and regenerative in mammalian organisms. In addition, the intestinal tissue is subject to adverse situations, where the balance between cell proliferation, differentiation and death has to be strictly maintained. However, the study of the cellular and developmental mechanisms that govern the development and architecture of the intestinal tissue is still in its infancy.

The general objective of our project focuses on understanding the determination and maintenance of intestinal functional domains, and to evaluate their spatiotemporal coordination.

More specifically, our aims are:

1. to define mechanisms controlling the integrity of the proliferative domain, and assess their impact on the crypt development;
2. to characterize the epithelial connectivity and collective behavior of the differentiated domain in homeostatic conditions or under challenging contexts.

One of the strong aspects of our research is to confront in vivo and in vitro murine and human disease models, and to combine different approaches from advanced cell biology, tissue engineering, histology, molecular biology, biophysics and computational modelling. This strategy allows us to determine the adaptive processes that epithelial cells employ to polarize and organize in a given environment, and enhance their ability to modulate their fate.

We are an interdisciplinary research unit with an important international openness and direct collaboration between cell biologists, biochemists and biophysicists.

We are combining classical biochemical and cell biology approaches with the development of new force microscopy nanotools to map the dynamics, interactions and mechanics of the cell membrane and its nanoenvironment. 

This interdisciplinary approach is developed at different scales, from the nanoscale of proteins and membranes to the microscale of cells and tissues, and at different timescales, from microseconds to minutes.