| First Author | Farin HF | Year | 2016 |
| Journal | Nature | Volume | 530 |
| Issue | 7590 | Pages | 340-3 |
| PubMed ID | 26863187 | Mgi Jnum | J:229237 |
| Mgi Id | MGI:5751329 | Doi | 10.1038/nature16937 |
| Citation | Farin HF, et al. (2016) Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature 530(7590):340-3 |
| abstractText | Mammalian Wnt proteins are believed to act as short-range signals, yet have not been previously visualized in vivo. Self-renewal, proliferation and differentiation are coordinated along a putative Wnt gradient in the intestinal crypt. Wnt3 is produced specifically by Paneth cells. Here we have generated an epitope-tagged, functional Wnt3 knock-in allele. Wnt3 covers basolateral membranes of neighbouring stem cells. In intestinal organoids, Wnt3-transfer involves direct contact between Paneth cells and stem cells. Plasma membrane localization requires surface expression of Frizzled receptors, which in turn is regulated by the transmembrane E3 ligases Rnf43/Znrf3 and their antagonists Lgr4-5/R-spondin. By manipulating Wnt3 secretion and by arresting stem-cell proliferation, we demonstrate that Wnt3 mainly travels away from its source in a cell-bound manner through cell division, and not through diffusion. We conclude that stem-cell membranes constitute a reservoir for Wnt proteins, while Frizzled receptor turnover and 'plasma membrane dilution' through cell division shape the epithelial Wnt3 gradient. |
