Secreted Wnt proteins act through a conserved pathway to control development.
Keywords: wingless; Wnt; Drosophila; frizzled; -catenin; Axin; APC; dishevelled
Signal Transduction Pathways in Development: Wnts and their Receptors
Roel Nusse, Stanford University, Stanford, California, USA
Published online: April 2001
DOI: 10.1038/npg.els.0002331
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Figure 1. The receptors for Wnt signals, the Frizzled proteins, consist of seven transmembrane segments and an amino-terminal cysteine-rich domain (CRD) that is outside the cell and binds the ligand.
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Figure 2. The Wnt signal transduction pathway. In the absence of Wnt signalling (a), the protein kinase Zw3/Gsk-3 inactivates Armadillo/-catenin (Arm), possibly by direct phosphorylation of Arm followed by proteolytic breakdown. The proteins Axin and APC are both also involved in downregulating Arm, by forming a complex with Arm and Zw3. In the nucleus, TCF acts as a repressor of target genes.
Wnt signalling (b) acts through a Frizzled (Fz) receptor on Dishevelled (Dsh), counteracting the activity of Zw3, resulting in stabilization and upregulation of the Arm protein. After Arm has escaped from negative regulation, it can act in the nucleus together with TCF to activate target genes. |
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| Further Reading | |
| Cadigan K and Nusse R (1997) Wnt signalling: a common theme in animal development. Genes and Development 11(24): 3286–3305. | |
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| Miller JR and Moon RT (1996) Signal transduction through -catenin and specification of cell fate during embryogenesis. Genes and Development 10(20): 2527–2539. | |
| Nusse R (1997) A versatile transcriptional effector of wingless signalling. Cell 89(3): 321–323. | |
| Perrimon N and McMahon AP (1999) Negative feedback mechanisms and their roles during pattern formation. Cell 97(1): 13–16. | |
| Polakis P (1997) The adenomatous polyposis coli (APC) tumor suppressor. Biochimica et Biophysica Acta – Reviews on Cancer 1332(3): F127–F147. | |
