Wynshaw-Boris A. Wnt signaling in mammalian development: lessons from mouse genetics. Cold Spring Harb Perspect Biol 2012; 4:a007963-[PMID

Wnts are evolutionarily conserved signaling ligands critical for animal development. Genetic engineering in the mouse has enabled investigators to acquire a detailed activation profile of the b-catenin-dependent canonicalWnt pathway duringmouse development, and to manipulate Wnt pathway activities with great spatial and temporal precision. Together, these studies have not only revealed important functions of Wnt signaling at multiple stages of early mouse development, but also elucidated how the Wnt pathway interacts with other pathways to form signaling networks that confer the unique features of mammalian embryo-genesis. Additionally, the planar cell polarity pathway has emerged as an essential b-catenin independent noncanonical Wnt pathway that coordinates cell polarity and regulates tissue morphogenesis in variousmammalian developmental processes. Importantly, studies ofWnt signaling in mouse development have also revealed important pathogenic mechanisms of several congenital disorders in humans. Among the model organisms used for study-ing Wnt signaling, the mouse shares the greatest genetic, structural, and physiological similarities with humans. Genetic studies in mice, therefore, provide the most direct insight in the role of Wnt signaling in human biology and diseases. Both mice and humans have 19 Wnt ligands and 10 Frizzled (Fz) receptors. Based on studies in Drosophila, Xenopus, and zebrafish, Wnt signaling can be broadly divided into the canonical Wnt pathway that involves b-catenin-mediated transcriptional activation, and the noncanonical Wnt pathway that is b-catenin independent but shares some compo-nents with the canonical Wnt pathway. In this review, we will discuss how both canonical and noncanonical Wnt signaling contributes to the unique developmental processes in mammals