作者
Henner F Farin, Ingrid Jordens, Mohammed H Mosa, Onur Basak, Jeroen Korving, Daniele VF Tauriello, Karin De Punder, Stephane Angers, Peter J Peters, Madelon M Maurice, Hans Clevers
发表日期
2016/2/18
期刊
Nature
卷号
530
期号
7590
页码范围
340-343
出版商
Nature Publishing Group UK
简介
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 …
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