TY - JOUR
T1 - Lgr4-deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3
AU - Mohri, Yasuaki
AU - Oyama, Kazunori
AU - Akamatsu, Atsushi
AU - Kato, Shigeki
AU - Nishimori, Katsuhiko
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
KW - Kidney morphogenesis
KW - Knockout mice
KW - Lgr4
KW - Ureteric bud
KW - Wnt canonical pathway
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U2 - 10.1002/dvdy.22651
DO - 10.1002/dvdy.22651
M3 - Article
C2 - 21523854
AN - SCOPUS:79955733257
VL - 240
SP - 1626
EP - 1634
JO - American Journal of Anatomy
JF - American Journal of Anatomy
SN - 1058-8388
IS - 6
ER -