Visualization of a short-range Wnt gradient in the intestinal stem-cell niche

Henner F Farin, Ingrid Jordens, Mohammed H Mosa, Onur Basak, Jeroen Korving, Daniele V F Tauriello, Karin de Punder, Stephane Angers, Peter J Peters, Madelon M Maurice, Hans Clevers

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

370 Citaten (Scopus)


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.

Originele taal-2Engels
Pagina's (van-tot)340-3
Aantal pagina's4
Nummer van het tijdschrift7590
StatusGepubliceerd - 18 feb. 2016


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