Mechanosensory hair cells in the zebrafish, and other nonmammalian vertebrates, are capable of regeneration after damage, whereas mammals are largely unable to regenerate hair cells. However, across vertebrates many of the same pathways are required for hair cell formation: Wnt/β-catenin signaling promotes proliferation of sensory progenitor cells and Fgf and Notch signaling activate and restrict expression of the prosensory transcription factor atoh1. atoh1 is also required for differentiation and hair cell maturation. The zebrafish lateral line is composed of mechanosensory organs (neuromasts) that are functionally analogous to the mechanoreceptors of the mammalian inner ear. Mature hairs cells within each neuromast are constantly replenished during homeostasis, and hair cell regeneration occurs rapidly after damage. We are using the zebrafish lateral line to dissect the roles of Wnt, Notch and Fgf signaling in support cell proliferation and hair cell differentiation during homeostasis and regeneration. Our previous work showed that in mature neuromasts, Notch and Wnt signaling balance support cell proliferation and hair cell differentiation. However, the genes regulated by these pathways during regeneration are still unknown. In mammalian tissues, the leucine-rich repeat-containing G-protein-coupled receptor (LGR) family members Lgr4/5/6 are stem cell markers in the intestinal epithelium, the hair follicle niche and the cochlea. In zebrafish, we have been unable to identify lgr5 by sequence similarity or phylogenetic analysis, but lgr4 and lgr6 are expressed during lateral line development. However, only lgr6 is expressed in support cells that surround lateral line hair cells in mature neuromasts. Our functional analyses using heatshock inducible and lgr6 mutant lines demonstrate that lgr6 is a Wnt target in mature neuromasts. Wnt/β-catenin promotes support cell proliferation after hair cell damage and our results suggest that Wnt/β-catenin regulates proliferation via Lgr6 during hair cell regeneration. Lgr6 is also regulated by Fgf and Notch signaling and our studies reveal a regulatory network between the Wnt, Fgf, Notch and Lgr6 pathways that balance proliferation and differentiation during homeostasis and regeneration. These findings are important for designing therapies to induce hair cell regeneration in mammals.