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Review
. 2008 Jul;38(7):1788-94.
doi: 10.1002/eji.200738118.

The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesis

Frank J T Staal  1 , Jyoti M Sen
Affiliations
Review

The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesis

Frank J T Staal et al. Eur J Immunol. 2008 Jul.

Abstract

The evolutionarily conserved canonical Wnt-beta-catenin-T cell factor (TCF)/lymphocyte enhancer binding factor (LEF) signaling pathway regulates key checkpoints in the development of various tissues. Therefore, it is not surprising that a large body of gain-of-function and loss-of-function studies implicate Wnt-beta-catenin signaling in lymphopoiesis and hematopoiesis. In contrast, recent papers have reported that Mx-Cre-mediated conditional deletion of beta-catenin and/or its homolog gamma-catenin (plakoglobin) did not impair hematopoiesis or lymphopoiesis. However, these studies also report that TCF reporter activity remains active in beta-catenin- and gamma-catenin-deficient hematopoietic stem cells and all cells derived from these precursors, indicating that the canonical Wnt signaling pathway was not abrogated. Therefore, these studies in fact show that the canonical Wnt signaling pathway is important in hematopoiesis and lymphopoiesis, even though the molecular basis for the induction of the reporter activity is currently unknown. In this perspective, we provide a broad background to the field with a discussion of the available data and create a framework within which the available and future studies may be evaluated.

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Conflict of interest statement

Conflict of interest: The authors declare no financial or commercial conflict of interest.

Figures

Figure 1
Figure 1
The canonical Wnt signaling pathway. (Left) In the absence of Wnt binding, β-catenin is sequestered in the cytoplasm by Axin and adenomous polyposis coli (APC). In this ‘destruction complex’, β-catenin is phosphorylated by serine/threonine kinases casein kinase (CK) and glycogen synthase kinase (GSK)3β. Phosphorylated β-catenin is recognized by β-transducin repeat-containing protein (β-TRCP), targeted for ubiquitination and degraded by the proteasome pathway. In the absence of β-catenin, TCF family transcription factors bind co-repressors of the groucho family. (Right) Wnt proteins bind to a receptor complex consisting of a frizzled receptor (Fz) and LRP5 or LRP6. Wnt signals are transduced to the destruction complex via as yet unknown pathway involving Dishevelled (DSH). DSH may directly interact with Fz and LRP may interact with Axin. Signaling inhibits GSK3β activity and β-catenin degradation. Accumulated β-catenin translocates to the nucleus to activate gene transcription in conjunction with TCF/LEF. γ-Catenin (plakoglobin), a structural homolog of β-catenin, also binds TCF/LEF transcription factors but is believed to provide a weaker transcriptional activation domain compared to β-catenin. This figure is adapted from the article by Weerkamp and colleagues [63].
Figure 2
Figure 2
Overview of reports documenting Wnt signaling in T cell development and HSC biology. References with a green bullet provide evidence favoring a role, while those labeled with a red bullet provide evidence against a role for canonical Wnt signaling.
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