Wnt transfer in the intestinal stem cell niche
Biochemistry
Final Report Abstract
Spatial and temporal control of Wnt delivery to the intestinal stem cell niche regulates intestinal homeostasis. Telocytes, specialized stromal cells with characteristic long thin cytoplasmic protrusions, produce essential Wnts for the development and maintenance of this niche. However, how Wnts travel from telocytes to stem cells in the gut remains controversial. To visualize specialized telocyte extensions that putatively secrete Wnts and make intimate contacts with epithelial cells via electron microscopy, telocytes transfected with an APEX-2 construct specifically designed to label the plasma membrane were co-cultured with intestinal organoids. In agreement with our findings from optical microscopy, serial section TEM confirmed that telocytes are found in close proximity to the basal membrane of organoid epithelial cells and that they form multiple podoms. Interestingly, filopodia-like extension branching off from the podoms could be visualized. Surprisingly, both the tips of podoms and the filopodia-like extensions formed close focal contacts with the epithelial cell surface. In addition, the epithelial cell surface appeared altered at the point of contact with the telocytes, suggesting that specialized morphological structures reminiscent of a signaling synapse are formed between the two cell types. Taken together, the data show that intestinal telocytes make close contacts with the basal membrane of epithelial cells both via the tips of podoms and filopodia to form synapse-like structures. This enables telocytes to transmit signals over long distances to the epithelial stem cells, putatively, to transport Wnt ligands for stem cell regulation.
Publications
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An itch for things remote: The journey of Wnts. Current Topics in Developmental Biology, 91-128.
Mittermeier, Lorenz & Virshup, David M.
