Grant: Operating Grant

The functional complexity of a multicellular organ such as the intestine involves a high degree of coordination among diverse specialized cell types. Maintaining this organization as well as regulation of intestinal cell functions requires a permanent and dynamic crosstalk between epithelial and underlying stromal cells. This crosstalk is mediated by crucial soluble factors such as the Bone Morphogenetic Proteins (Bmps). Bmp signaling within the intestine is complex: Bmps and their receptors are expressed in both epithelial and mesenchymal compartments, suggesting bidirectional signaling between the mesenchyme and the epithelium. The use of genetically modified mice is a powerful tool to establish significant advancement in the understanding of the in vivo function of a molecule of interest, especially in the context of intestinal epithelial-mesenchymal interactions. The main objective of this research proposal is to explore the distinct and specific contribution of mesenchymal and epithelial Bmp signaling components on intestinal epithelial functions and pathologies. This research proposal will unravel the mechanisms underlying the distinctive contribution of both the mesenchyme and epithelium to the homeostasis of the intestinal mucosa in health and disease Improving our knowledge of the spatial and temporal control of gastrointestinal cell functions might ultimately contribute to developing cell-based therapies for pathologies such as the inflammatory bowel diseases and colorectal cancer.