G‐protein coupled receptor‐54 is required for embryonic kidney branching morphogenesis and glomerular development through regulating Bmp7 expression

Abstract

Kidney branching morphogenesis and glomerular development are two key processes in embryonic kidney formation. Bmp7 has been identified to be essential for these processes. However, the molecular mechanism of regulating Bmp7 expression in kidneys has not been fully understood. Here we report that G‐protein coupled receptor 54 (Gpr54) regulates Bmp7 expression and is required for mouse embryonic kidney development. Gpr54 deletion leads to severely retarded kidney branching morphogenesis, S‐shaped body formation, glomerular development, and nephron underdosing in embryonic kidneys in vivo and in explanted kidneys in vitro. Deletion of Gpr54 significantly decreases Bmp7 expression in developing kidneys. Using CHIP and luciferase assays, we demonstrate that Gpr54 regulates NFAT2, but not NFAT1, NFAT3 or NFAT4, mediated Bmp7 transcription. Furthermore, we show that Gpr54 regulates Sp1, but not phosphorylated Sp1, mediated Bmp7 transcription. Together, these data suggest that Gpr54 signaling pathway regulate Bmp7 expression and play important roles in embryonic kidney branching morphogenesis and development. Gpr54 could be a new therapeutic target for kidney diseases.