Lgr4‐deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3

We previously reported that Lgr4 has a critical role in the morphogenesis of kidney, but the detailed functions of Lgr4 in kidney development have not been elucidated. In contrast to Lgr4 null mice with 129Ola × C57BL/6J mixed background, C57BL/6J‐backcrossed Lgr4 null mice (Lgr4−/−) showed the severe phenotype of embryonic lethality and also had dilated tubules in kidneys at E16.5. Based on quantitative RT‐PCR and in situ hybridization, branching morphogenesis at E15.5 in the Lgr4−/− was arrested earlier, and both DBA‐lectin staining and immunohistochemical analysis using Aqp3 antibodies showed that the ureteric bud (UB) of Lgr4−/− kidneys underwent premature differentiation. Furthermore, quantitative RT‐PCR and histological analysis suggested that the impaired UB differentiation was caused by down‐regulation of the Wnt pathway and Gata3 in the Lgr4−/− kidneys. We demonstrate here that Lgr4 has a novel function for maintaining the UB in an undifferentiated state. Developmental Dynamics 240:1626–1634, 2011. © 2011 Wiley‐Liss, Inc.