Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors.

Signaling pathways are an ever present force in every animal’s life. During development, these pathways provide critical cell-cell communication required to coordinate the activities of vast numbers of cells. In adulthood, similar communication mechanisms are utilized to achieve tissue homeostasis and regeneration. Regulation of signaling is crucial; toomuch or too little activity from a given signal transduction pathway can cause devastating results such as developmental defects or, later in life, disease. The Wnts comprise a large family of highly conserved growth factors that are responsible for important developmental and homeostatic processes throughout the animal kingdom (for a more comprehensive review see Ref. 1). Their implication in a wide array of developmental events and humandiseases hasmade Wnts and their signaling pathways the subject of intense investigation over the last two decades. This has never been truer than in the past few years, when the association of Wnt signaling with stem cell fate has added fuel to an already active field. Membership in the Wnt family is defined by amino acid sequence rather than functional properties. It is therefore not too surprising thatWnts have been associatedwith a number of different activities and downstream signaling pathways. Although the majority of work in the field to date has focused on -catenin-dependent, or canonical, Wnt signaling, examples continue to accumulate in which Wnts and/or other key components of the canonical signaling cascade participate in -catenin-independent processes (reviewed in Ref. 2). In this review, we will focus largely on the canonical pathway, paying particular attention to recent insights. We will then touch on some developments in -catenin-independent signaling and discuss some issues that may be important to all Wnts, regardless of the signal they generate.