Drosophila Wnt/Fz pathways

Abstract

Wnts [also known as Wingless (Wg)] are a family of conserved signaling molecules involved in a plethora of fundamental developmental and cell biological processes, such as cell proliferation, differentiation, and cell polarity. Dysregulation of the pathway can be detrimental, because several components are tumorigenic when mutated and are associated with hepatic, colorectal, breast, and skin cancers. First identified in the fruit fly Drosophila melanogaster as a gene family responsible for patterning the embryonic epidermis, the Wnt gene family, including Wg, encode secreted glycoproteins that activate receptor-mediated signaling pathways leading to numerous transcriptional and cellular responses. The main function of the canonical Wg pathway is to stabilize the cytoplasmic pool of a key mediator, beta-catenin [beta-catenin, known as Armadillo (Arm) in fruit flies], which is otherwise degraded by the proteasome pathway. Initially identified as a key player in stabilizing cell-cell adherens junctions, Arm is now known to also act as a transcription factor by forming a complex with the lymphoid enhancer factor (LEF)/T cell-specific transcription factor (TCF) family of high mobility group (HMG)-box transcription factors. Upon Wnt/Wg stimulation, stabilized Arm translocates to the nucleus, where, together with LEF/TCF transcription factors, it activates downstream target genes that regulate numerous cell biological processes.