Nephron, Wilms' tumor-1 (WT1), and synaptopodin expression in developing podocytes of mice.
Newborn mouse glomeruli are still immature with a morphological feature of an early capillary loop stage, but infant mice do not manifest proteinuria. Little is known about the molecular mechanism whereby infant mice are resistant to proteinuria. Nephrin and synaptopodin are crucial for slit diaphragm and foot process (FP) formation for avoiding proteinuria. Nephrin tyrosine phosphorylation means a transient biological signaling required for FP repair or extension during nephrotic disease. Using an immunohistochemical technique, we examined the natural course of nephrin, Wilms' tumor-1 (WT1) and synaptopodin at 16.5 days of embryonic age (E16.5d) and E19.5d, 7 days of post-neonatal age (P7d) and P42d during renal development of mice. As a result, nephrin and synaptopodin were detected at E19.5d in S-shaped bodies. WT1, a transcriptional factor for nephrin, was detected in nucleus in podocyte-like cells in all stages. Nephrin tyrosine phosphorylation was evident in glomeruli at P7d, and this was associated with an early-stage of FP extension. Inversely, nephrin phosphorylation became faint at P42d, along with maturated FP. Based on the present results, we suggest the sequential molecular mechanism to protect growing mice from proteinuria: (i) WT1-induced nephrin production by podocytes in S-shaped bodies at E19.5d; (ii) Synchronized induction of synaptopodin at the same period; and (iii) FP extension is initiated at a milk-suckling stage under a nephrin tyrosine-phosphorylated condition, while it is arrested at an adult stage, associated with a loss of nephrin-based signaling.
Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.|Department of Pathology, Faculty of Medicine, Kindai University, 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, Japan.
Takashi
T
Kato
Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.|Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Shinya
S
Mizuno
D000818:Animals; D000831:Animals, Newborn; D015870:Gene Expression; D007678:Kidney Glomerulus / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D025721:WT1 Proteins
D008565:Membrane Proteins; D008840:Microfilament Proteins; D012097:Repressor Proteins; C503968:Synpo protein, mouse; D025721:WT1 Proteins; C000602896:WT1 protein, mouse; C113267:nephrin
Wilms’ tumor-1 (WT1); glomerulogenesis; nephrin; podocyte; synaptopodin