Abstract
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 language | English |
|---|---|
| Pages (from-to) | 305-16 |
| Number of pages | 12 |
| Journal | Genes & Development |
| Volume | 28 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 15 Feb 2014 |
Keywords
- Animals
- Embryonic Development
- Gene Expression Regulation
- Humans
- Receptors, G-Protein-Coupled
- Signal Transduction
- Thrombospondins
- Ubiquitin-Protein Ligases
- Wnt Signaling Pathway