Wnt Signaling Pathways

Wnt Gene Family

The Wnt family consists of a number of highly conserved genes that regulate gene expression, cell behavior, cell adhesion, and cell polarity, including 19 genes in humans and mice, 7 in Drosophila, and 5 in C. elegans. Wnt-1 is one member of a gene family whose additional members were isolated either as a target for MMTV insertion (Wnt-3, Wnt-3A was subsequently isolated by homology to Wnt-3), fortuitously from a chromosomal walk directed around the cystic fibrosis gene (Wnt-2), or from mouse embryo RNA using the polymerase chain reaction (Wnt-4, -5A, -5B, -6, -7A, and -7B)....

Wnt Signaling Pathways

The Wnt signaling pathway is a conserved pathway. The Wnt family of signaling proteins participates in multiple developmental events during embryogenesis and has also been implicated in adult tissue homeostasis. Wnt signals are pleiotropic, with effects that include mitogenic stimulation, cell fate specification, and differentiation....

Canonical Wnt Pathway

The canonical Wnt pathway (or Wnt/β-catenin pathway) is the Wnt pathway that causes an accumulation of β-catenin in the cytoplasm and its eventual translocation into the nucleus to act as a transcriptional coactivator of transcription factors that belong to the TCF/LEF family. Without Wnt, β-catenin would not accumulate in the cytoplasm since a destruction complex would normally degrade it....

Non-Canonical Wnt Pathways

Intracellular signaling of the Wnt pathway diversifies into at least three branches:...

Wnt Pathway Regulation

One key level of regulation of Wnt signaling occurs in the extra-cellular milieu with the presence of a diverse number of secreted Wnt antagonists. After binding of Wnt to the receptor complex, the signal is transduced to cytoplasmic phosphoprotein Dishevelled (Dsh/Dvl), and studies have uncovered that Dsh can directly interact with Fz(frizzled). At the level of Dsh(Dishevelled), the Wnt signal branches into at least three major cascades, canonical, Planar Cell Polarity, and Wnt/Ca2+. Dsh (Dishevelled) is an important downstream component of this transduction pathway and is the first cytoplasmic protein that is pivotally involved in all three major branches of Wnt signaling. The Wnt ligands are secreted glycoproteins that are heavily modified prior to transport and release into the extra-cellular milieu....

Functions of Wnt Proteins in Polarity Orientation

At least for some cells, Wnts can instruct the polarity orientation by functioning as a positional signal. Recent genetic analyses have suggested that Wnt can also control cell polarity from a distance. For example, CWN-1 and CWN-2 (Common Wire Nail – CWN) are respectively expressed posteriorly and anteriorly with regard to the seam cells and control the seam cells’ polarity orientation. In addition to Wnts, mutants of some Wnt receptors cause polarity reversal with some frequency, consistent with the notion that they mediate the functions of Wnts. For example, the polarity of the V1 seam cell is reversed in cam-1/Ror (a non-Fz type Wnt receptor with a tyrosine kinase domain) The T cell polarity can be reversed in lin-17/Fz mutants, although the loss of polarity is a more frequent outcome. In addition, Wnt receptors are essential for cell polarization itself, since the polarity of embryonic cells and postembryonic seam cells are lost in mom-5( (Frizzled type Wnt receptor)) single and lin-17 mom-5( (Frizzled type Wnt receptor)) cam-1 triple mutant, respectively. Although Wnts are involved in many asymmetric divisions, those of the SGPs (somatic gonadal precursors; Z1 and Z4 cells) appear to be Wnt independent, since their polarity is not affected in quintuple Wnt mutants....

FAQs on Wnt Signaling

Question 1: Define Wnt Signaling....