The R-spondin/Lgr5/Rnf43 module: regulator of Wnt signal strength

Wim de Lau, Weng Chuan Peng, Piet Gros, Hans Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

427 Citations (Scopus)


Lgr5 was originally discovered as a common Wnt target gene in adult intestinal crypts and colon cancer. It was subsequently identified as an exquisite marker of multiple Wnt-driven adult stem cell types. Lgr5 and its homologs, Lgr4 and Lgr6, constitute the receptors for R-spondins, potent Wnt signal enhancers and stem cell growth factors. The Lgr5/R-spondin complex acts by neutralizing Rnf43 and Znrf3, two transmembrane E3 ligases that remove Wnt receptors from the stem cell surface. Rnf43/Znrf3 are themselves encoded by Wnt target genes and constitute a negative Wnt feedback loop. Thus, adult stem cells are controlled by an intricate interplay of potent Wnt agonists, antagonists, and anti-antagonists.

Original languageEnglish
Pages (from-to)305-16
Number of pages12
JournalGenes & Development
Issue number4
Publication statusPublished - 15 Feb 2014


  • Animals
  • Embryonic Development
  • Gene Expression Regulation
  • Humans
  • Receptors, G-Protein-Coupled
  • Signal Transduction
  • Thrombospondins
  • Ubiquitin-Protein Ligases
  • Wnt Signaling Pathway


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