Controlling Wnt Signaling Specificity and Implications for Targeting WNTs Pharmacologically

Wnt signaling is critical for proper development of the embryo and for tissue homeostasis in the adult. Activation of this signaling cascade is initiated by binding of the secreted Wnts to their receptors. With the mammalian genome encoding multiple Wnts and Wnt receptors, a longstanding question in the field has been how Wnt-receptor specificities are achieved. Emerging from these studies is a picture of exquisite control over Wnt protein production, secretion, distribution, and receptor interactions, culminating in activation of downstream signaling cascades that control a myriad of biological processes. Here we discuss mechanisms by which Wnt protein activities are tuned and illustrate how the multiple layers of regulation can be leveraged for therapeutic interventions in disease.