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 3 C57BL/6J mixed background, C57BL/6J-backcrossed Lgr4 null mice (Lgr4 2/2 ) 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 2/2 was arrested earlier, and both DBAlectin staining and immunohistochemical analysis using Aqp3 antibodies showed that the ureteric bud (UB) of Lgr4 2/2 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 2/2 kidneys. We demonstrate here that Lgr4 has a novel function for maintaining the UB in an undifferentiated state. Developmental Dynamics 240:1626-1634,

No abstract

In mice, homozygous Lgr4 inactivation results in hypoplastic kidneys. To understand better the role of LGR4 in kidney development, we performed an analysis of kidneys in Lgr4-/- embryos. We stained Lgr4-/- kidneys with anti-WT1 and anti-Cleaved Caspase3 antibodies at E16.5, and observed that the structures of the cap mesenchyme were disrupted and that apoptosis increased. In addition, the expression of PAX2, an anti-apoptotic factor in kidney development, was also significantly decreased at E16.5. We found that the LGR4 defect caused an increase in apoptosis in the peripheral mesenchyme during kidney development.