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WNT signaling pathway

Thursday 10 July 2003

WNT signalling has a key role in early embryonic patterning through the regulation of cell fate decisions, tissue polarity and cell movements.

Wnt signal transduction is crucial for maintaining the balance between proliferation and differentiation throughout embryogenesis and postnatal life.

Functions

- In the vertebrate embryo, the formation of the dorsal-ventral axis depends on the activity of the Wnt signaling pathway.

- In the nervous system, WNT signalling regulates neuronal connectivity by controlling axon pathfinding, axon remodelling, dendrite morphogenesis and synapse formation.

Components

WNT1 CTNNB1 AXIN1 AXIN2

Pathology of the Wnt/beta-catenin pathway

- cancer predisposition

  • colonic cancer predisposition
    - mutations in AXIN2 predispose to colonic adenocarcinoma (#15042511#)

- developmental anomalies

  • mutations in AXIN2 in familial tooth agenesis (#15042511#)

- RSPO4 germline mutations in inherited anonychia and hyponychia congenita (MIM.206800) (#17186469#, #17041604#)

  • Anonychia is an autosomal recessive disorder characterized by the congenital absence of finger- and toe-nails.
  • RSPO4 is a member of the recently described R-spondin family of secreted proteins that play a major role in activating the Wnt/ beta -catenin signaling pathway.

References

- Cadigan KM, Liu YI. Wnt signaling: complexity at the surface. J Cell Sci 2006;119:395–402.

- Tycko B, Li CM, Buttyan R. The Wnt/beta-catenin pathway in Wilms tumors and prostate cancers. Curr Mol Med. 2007 Aug;7(5):479-89. Review. PMID: #17691963#

- van Amerongen R, Berns A. Knockout mouse models to study Wnt signal transduction. Trends Genet. 2006 Oct 10; PMID: #17045694#

- Brembeck FH, Rosario M, Birchmeier W. Balancing cell adhesion and Wnt signaling, the key role of beta-catenin. Curr Opin Genet Dev. 2006 Feb;16(1):51-9. PMID: #16377174#

- Ciani L, Salinas PC. WNTS in the vertebrate nervous system: from patterning to neuronal connectivity. Nat Rev Neurosci. 2005 May;6(5):351-62. PMID: #15832199#

- Gregorieff A, Clevers H. Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev. 2005 Apr 15;19(8):877-90. PMID: #15833914#

- Audrey Koay M, Brown MA. Genetic disorders of the LRP5-Wnt signalling pathway affecting the skeleton. Trends Mol Med. 2005 Mar;11(3):129-37. PMID: #15760771#

- Moon RT, Kohn AD, De Ferrari GV, Kaykas A. WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet. 2004 Sep;5(9):691-701. PMID: #15372092#

- Clevers H. Wnt signaling: Ig-norrin the dogma. Curr Biol. 2004 Jun 8;14(11):R436-7. PMID: #15182694#

- Wang J, Wynshaw-Boris A. The canonical Wnt pathway in early mammalian embryogenesis and stem cell maintenance/differentiation. Curr Opin Genet Dev. 2004 Oct;14(5):533-9. PMID: #15380245#

- Tolwinski NS, Wieschaus E. Rethinking WNT signaling. Trends Genet. 2004 Apr;20(4):177-81. PMID: #15041171#

- Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science. 2004 Mar 5;303(5663):1483-7. PMID: #15001769#

- Kalderon D. Similarities between the Hedgehog and Wnt signaling pathways. Trends Cell Biol. 2002 Nov ;12(11):523-31. PMID : #12446114#

- Kuhl M, Sheldahl LC, Park M, Miller JR, Moon RT. The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet. 2000 Jul;16(7):279-83. PMID: #10858654#

- Nusse R. WNT targets. Repression and activation. Trends Genet. 1999 Jan ;15(1):1-3. PMID : #10087922#