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 tijdschriftArtikelpeer review

371 Citaten (Scopus)

Samenvatting

Mammalian Wnt proteins are believed to act as short-range signals1-4, yet have not been previously visualized in vivo. Selfrenewal, proliferation and differentiation are coordinated along a putative Wnt gradient in the intestinal crypt5. Wnt3 is produced specifically by Paneth cells6,7. Here we have generated an epitopetagged, 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)340-343
Aantal pagina's4
TijdschriftNature
Volume530
Nummer van het tijdschrift7590
DOI's
StatusGepubliceerd - 18 feb. 2016
Extern gepubliceerdJa

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