During my PhD thesis, I explored the role of cell mechanics in the development and maintenance of the small intestinal epithelium. I focused on two main areas. First, my colleagues and I discovered novel structures called actin stars (AcSs) within the basal domain of differentiated epithelial cells. These star-shaped actomyosin networks are critical for maintaining the stability of epithelial tissue by optimizing cell hexagonality and packing, which helps preserve the solid-like structure of the epithelium and avoid lamellipodia-like protrusions to develop. The AcS network also plays a significant role in ensuring long-range connectivity and spatial coordination among cells, thus supporting the architecture of the differentiated domain of the intestine.
Secondly, I investigated the role of EpCAM, a protein known for its involvement in epithelial contractility, in the process of crypt formation and maintenance. Through studies on both patient biopsies and EpCAM knock-out mouse organoids, I demonstrated that the loss of EpCAM leads to abnormal crypt morphology, disrupted cell homeostasis, and an increase in asymmetric crypt fissions. This highlights the importance of EpCAM in maintaining proper tension and organization within the Paneth cell/stem cell niche at the base of the crypts, which is crucial for correct crypt fission and overall tissue remodeling.
Overall, this research provides new insights into the mechanisms of intestinal epithelial morphogenesis and homeostasis, contributing to a deeper understanding of how the small intestinal epithelium is established, compartmentalized, and maintained.