PhD Discussions: Gerardo Ceada Torres

Role of Eph/Ephrin in the Compartmentalization of the Intestinal Stem Cell Niche

Gerardo Ceada Torres, Integrative cell and tissue dynamics Group

The intestinal epithelium is a monolayer of cells that covers the inner surface of the gut. It protects against pathogens, absorbs nutrients, and secretes hormones and other molecules. This monolayer is folded into finger-like protrusions composed of differentiated cells, called villi, and invaginations, called crypts, where stem cells reside. Essential features of the intestinal epithelium such as folding of the crypt, spatial distribution of different cell types, and cellular movements from crypt to villus-like domains can be recapitulated in vitro in intestinal organoids. Direct force measurements in mouse intestinal organoids grown on soft hydrogels show that tightly regulated cell-ECM and cell-cell forces compartmentalizes the tissue into crypts- and villus-like domains. A dynamic mechanical boundary composed of basally constricted cells is established between the stem cell niche and differentiated cells of the villus-like region. The Eph/Ephrin signaling pathway has been proposed as a key regulator of compartmentalization and cell positioning in the intestinal epithelium. Whether and how Eph/Ephrin signaling governs the mechanical phenotype observed at the crypt-villus boundary remains, however, an open question. We are currently addressing this question by genetically perturbing Eph/Ephrin signaling in intestinal organoids. Preliminary data show that EphB2/3 KO organoids display defects in cell positioning, reduced basal constriction at the crypt-villus boundary and aberrant size of the proliferative and differentiated compartments.

This PhD Discussion session will be held at Tower I, 11th floor Baobab room, at 10:00am.

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