P110. Visinin like 1 is differentially expressed in ureteric tips upon induction or disruption of branching

The tip of the ureteric bud in the metanephric kidney is a signaling center inducing formation of mesenchyme-derived nephrons, and simultaneously it responds by growth and branching to signals from the mesenchyme. Here we report that Visinin like 1 (Vsnl1) is a new ureteric bud tip marker, which encodes for a neuronal calcium sensor—Vsnl1 protein with a mosaic expression pattern in the kidney. Mice deficient for glial-cell-line-derived neurotrophic factor (GDNF), which is essential for ureteric bud outgrowth and subsequent branching, lack Vsnl1 in UB. Vsnl1 mRNA and protein expression is restored in these kidney explants not only by exogenous GDNF, but also by alternative bud inducers FGF/Follistatin, which also induce Vsnl1 positive supernumerary buds in GDNF receptor Ret-null kidneys. Hence, Vsnl1 characterizes the ureteric bud tip epithelium regardless of the inducer, also in the absence of Ret. Increased intracellular calcium has been shown to have an antagonistic effect on β-catenin activity, whereas Vsnl1 is a calcium binding protein and co-localizes with intracellular calcium release in the UB. Our data show that Vsnl1 compromises β-catenin stability in mouse collecting duct cells and that it may interact with Wnt/β-catenin signaling also in the developing kidney, as Vsnl1 expression is downregulated or strongly reduced in β-catenin gain or loss of function in the ureteric epithelium.