2007 Fiscal Year Final Research Report Summary
Comprehensive analysis of the factor in connection with ureteric bud branching of the initial metanephros of mouse embryos
| Project/Area Number |
17590179
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | Fujita Health University |
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Principal Investigator |
HASEGAWA Yoshimi Fujita Health University, School of Medicine, Anatomy, Research Assistant (40288494)
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| Co-Investigator(Kenkyū-buntansha) |
NOMURA Ryuji Fujita Health University, School of Medicine, Anatomy, Assistant Professor (20325161)
SHIMOMURA Atsushi Fujita Health University, School of Medicine, Anatomy, Research Assistant (50340237)
KOGO Akiko Fujita Health University, School of Medicine, Anatomy, Research Assistant (20340242)
YAMADA Koji Fujita Health University, School of Medicine, Anatomy, Assistant Professor (60278306)
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| Project Period (FY) |
2005 – 2007
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| Keywords | ICAT / Wnt signaling pathway / ureteric bud branching / renal agenesis |
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| Research Abstract |
The Wnt signals, which are critical for embryonic development in vertebrates, stabilize β-catenin and localize it in the nucleus. T cell factor/lymphoid enhancer factor (TCF/LEF) protein mediates the transcriptional regulation of Wnt/β-catenin target genes that play critical roles in cell growth, proliferation and differentiation. ICAT, inhibitor of β-catenin and T cell factor, is a negative regulator of the Wnt signaling pathway that interferes with the interaction between β-catenin and T cell factor. We used knockout mice of null mutation in the ICAT gene. ICAT-deficient (ICAT^<-/->) embryos exhibited malformation of the forebrain and craniofacial bones. Furthermore, renal agenesis was found in 13% of ICAT^<-/-> embryos. Some ICAT^<-/-> embryos exhibit unilateral or bilateral renal agenesis. In this study, we searched developmental processes in the ICAT^<-/-> kidney.
ICAT was highly expressed in both the ureteric bud (UB) and the surrounding metanephric mesenchymal (MM) cells in the m
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etanephros of embryonic day E11.5-E13.5 wild-type (ICAT^<+/+>) mouse. We next performed whole-mount immunostaining of E12.5 metanephros for cytokeratin to visualize UB branching. The number of UB tips in the metanephros was ICAT^<-/-> metanephroi, whereas in the ICAT^<+/-> metanephroi, with a significant difference. In the E12.5-ICAT^<-/-> metanephros, UB branching was delayed, and a T-shaped, bifurcated UB was frequently seen; this was never seen in the E12.5-ICAT^<+/-> metanephros. This indicates that the UB branching was disturbed and arrested at the T-shaped stage in some ICAT^<-/-> metanephroi. Next study, apoptotic cells in metanephroi were detected by a TUNEL assay around the T-shaped stage, in ICAT^<-/-> and ICAT^<+/+> embryos. More apoptotic MM cells were detected in the ICAT^<-/->metanephros than in the ICAT^<+/+> metanephros. These results suggest that the loss of ICAT gene function causes the arrest of UB branching and the apoptotic death of MM cells, resulting in renal agenesis. Less
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Research Products
(10 results)
