title: Lgr4-deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3.
abstract: 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.
authors.affiliation: Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Mohri
authors.forename: Kazunori
authors.initials: K
authors.lastname: Oyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Akamatsu
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kato
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nishimori
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D014513:Ureter / Q000196:embryology* / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C496200:LGR4 protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins