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. 2008 Apr;4(2):68-75.
doi: 10.4161/org.4.2.5851.

Wnt signal transduction pathways

Affiliations

Wnt signal transduction pathways

Yuko Komiya et al. Organogenesis. 2008 Apr.

Abstract

The Wnt signaling pathway is an ancient and evolutionarily conserved pathway that regulates crucial aspects of cell fate determination, cell migration, cell polarity, neural patterning and organogenesis during embryonic development. The Wnts are secreted glycoproteins and comprise a large family of nineteen proteins in humans hinting to a daunting complexity of signaling regulation, function and biological output. To date major signaling branches downstream of the Fz receptor have been identified including a canonical or Wnt/beta-catenin dependent pathway and the non-canonical or beta-catenin-independent pathway which can be further divided into the Planar Cell Polarity and the Wnt/Ca(2+) pathways, and these branches are being actively dissected at the molecular and biochemical levels. In this review, we will summarize the most recent advances in our understanding of these Wnt signaling pathways and the role of these pathways in regulating key events during embryonic patterning and morphogenesis.

Keywords: Planar Cell Polarity; Wnt; canonical; dishevelled; frizzled; non-canonical; β-catenin.

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Figures

Figure 1
Figure 1
A schematic representation of the canonical Wnt signal transduction cascade. Left, in the absence of Wnt ligand, a complex of Axin, APC, GSK3-β, CK1 and β-catenin is located in the cytosol. β-catenin is dually phosphorylated by CK1 and GSK3-β and targeted degraded by the proteosomal machinery mediated by β-TrCP. Right, with Wnt stimulation, signaling through the Fz receptor and LRP5/6 co-receptor complex induces the dual phosphorylation of LRP6 by CK1 and GSK3-β and this allows for the translocation of a protein complex containing Axin from the cytosol to the plasma membrane. Dsh is also recruited to the membrane and binds to Fz and Axin binds to phosphorylated LRP5/6. This complex formed at the membrane at Fz/LRP5/6 induces the stabilization of β-cat via either sequestration and/or degradation of Axin. β-catenin translocates into the nucleus where it complexes with Lef/Tcf family members to mediate transcriptional induction of target genes.
Figure 2
Figure 2
A schematic representation of the Planar Cell Polarity transduction cascade. Wnt signaling is transduced through Fz independent of LRP5/6 leading to the activation of Dsh. Dsh through Daam1 mediates activation of Rho which in turn activates Rho kinase (ROCK). Daam1 also mediates actin polymerization through the actin binding protein Profilin. Dsh also mediates activation of Rac, which in turn activates JNK. The signaling from Rock, JNK and Profilin are integrated for cytoskeletal changes for cell polarization and motility during gastrulation.
Figure 3
Figure 3
A schematic representation of the Wnt/Ca2+ signal transduction cascade. Wnt signaling via Fz mediates activation of Dsh via activation of G-proteins. Dishevelled activates the phosphodiesterase PDE which inhibits PKG and in turn inhibits Ca2+ release. Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin. Calcineurin activate NF-AT to regulate ventral cell fates. CamK11 activates TAK and NLK, which inhibit β-catenin/TCF function to negatively regulate dorsal axis formation. DAG through PKC activates CDC42 to mediate tissue separation and cell movements during gastrulation.

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