Limits...
High expression of Pitx-2 in the ICAT-deficient metanephros leads to developmental arrest.

Hasegawa Y, Iizuka-Kogo A, Akiyama T, Senda T - Acta Histochem Cytochem (2010)

Bottom Line: In order to examine the process of this developmental defect, molecular changes were analyzed in fetal ICAT-/- kidneys with a focus on Wnt-signaling associated factors.There was no genotypic difference in the expression level of another Wnt target gene, c-Ret.In the ICAT-/- kidneys which developed to E18.5 without any apparent defect, renal glomeruli, convoluted tubules and collecting ducts were decreased in density and showed abnormal structure.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy I, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.

ABSTRACT
ICAT (Inhibitor of β-catenin and T cell factor) inhibits the interaction between β-catenin and TCF/LEF transcription factor and serves as a negative regulator of Wnt signaling. In a subset of ICAT knockout mice, significant delay in the ureteric bud branching and renal agenesis are observed. In order to examine the process of this developmental defect, molecular changes were analyzed in fetal ICAT-/- kidneys with a focus on Wnt-signaling associated factors. The protein level of active β-catenin was elevated in ICAT-/- kidneys. DNA microarray and immunohistochemical analyses revealed that the expression of a Wnt target gene Pitx-2 was enhanced in ICAT-/- kidneys. There was no genotypic difference in the expression level of another Wnt target gene, c-Ret. These results suggest that the enhancement of Pitx-2 expression induced by activated Wnt signaling leads to delays in ureteric bud branching and subsequent renal agenesis. In the ICAT-/- kidneys which developed to E18.5 without any apparent defect, renal glomeruli, convoluted tubules and collecting ducts were decreased in density and showed abnormal structure. ICAT may be required for various developmental stages during renal development.

No MeSH data available.


Related in: MedlinePlus

Delay of the ureteric bud branching in ICAT−/− mice. (A, B) Whole mount immunostaining for cytokeratin showing ureteric bud branching at E12.5. A: ICAT+/− kidney. A ureteric bud normally branches making 7 tips. B: ICAT−/− kidney. T-shaped ureteric bud after first branching with abnormally dilated tips. An arrow indicates Wolffian duct. Bar=200 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2875859&req=5

Figure 1: Delay of the ureteric bud branching in ICAT−/− mice. (A, B) Whole mount immunostaining for cytokeratin showing ureteric bud branching at E12.5. A: ICAT+/− kidney. A ureteric bud normally branches making 7 tips. B: ICAT−/− kidney. T-shaped ureteric bud after first branching with abnormally dilated tips. An arrow indicates Wolffian duct. Bar=200 µm.

Mentions: As heterozygous (ICAT+/−) mice showed the same phenotype as wild type (ICAT+/+) mice, we used the wild type and the heterozygous mice as the control in this study. The number of tips of ureteric bud in kidneys of ICAT+/− mice at E12.5 was 5.93±1.09 (mean±standard deviation), whereas that of ICAT−/− mice was 4.49±1.14 (p<0.001), revealing that the number of ureteric bud branching in ICAT−/− mice was significantly low (Fig. 1A, B; [2]). In particular a T-shaped ureteric bud with two tips, which was never seen in ICAT+/+ mice at E12.5, was observed in 22.2% of the kidneys of ICAT−/− mice (Fig. 1B; [2]). Therefore, we speculated that the delayed ureteric bud branching in ICAT−/− kidneys led to apoptosis of non-aggregated mesenchymal cells around the ureteric bud, and that half of the ICAT−/− kidneys with T-shaped ureteric bud may not develop further, resulting in renal deficiency [2]. However, since the size of the kidneys (long axis) in ICAT−/− mice was statistically not reduced at E13.5 (data not shown), the effect of apoptosis may not appear until later stages.


High expression of Pitx-2 in the ICAT-deficient metanephros leads to developmental arrest.

Hasegawa Y, Iizuka-Kogo A, Akiyama T, Senda T - Acta Histochem Cytochem (2010)

Delay of the ureteric bud branching in ICAT−/− mice. (A, B) Whole mount immunostaining for cytokeratin showing ureteric bud branching at E12.5. A: ICAT+/− kidney. A ureteric bud normally branches making 7 tips. B: ICAT−/− kidney. T-shaped ureteric bud after first branching with abnormally dilated tips. An arrow indicates Wolffian duct. Bar=200 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2875859&req=5

Figure 1: Delay of the ureteric bud branching in ICAT−/− mice. (A, B) Whole mount immunostaining for cytokeratin showing ureteric bud branching at E12.5. A: ICAT+/− kidney. A ureteric bud normally branches making 7 tips. B: ICAT−/− kidney. T-shaped ureteric bud after first branching with abnormally dilated tips. An arrow indicates Wolffian duct. Bar=200 µm.
Mentions: As heterozygous (ICAT+/−) mice showed the same phenotype as wild type (ICAT+/+) mice, we used the wild type and the heterozygous mice as the control in this study. The number of tips of ureteric bud in kidneys of ICAT+/− mice at E12.5 was 5.93±1.09 (mean±standard deviation), whereas that of ICAT−/− mice was 4.49±1.14 (p<0.001), revealing that the number of ureteric bud branching in ICAT−/− mice was significantly low (Fig. 1A, B; [2]). In particular a T-shaped ureteric bud with two tips, which was never seen in ICAT+/+ mice at E12.5, was observed in 22.2% of the kidneys of ICAT−/− mice (Fig. 1B; [2]). Therefore, we speculated that the delayed ureteric bud branching in ICAT−/− kidneys led to apoptosis of non-aggregated mesenchymal cells around the ureteric bud, and that half of the ICAT−/− kidneys with T-shaped ureteric bud may not develop further, resulting in renal deficiency [2]. However, since the size of the kidneys (long axis) in ICAT−/− mice was statistically not reduced at E13.5 (data not shown), the effect of apoptosis may not appear until later stages.

Bottom Line: In order to examine the process of this developmental defect, molecular changes were analyzed in fetal ICAT-/- kidneys with a focus on Wnt-signaling associated factors.There was no genotypic difference in the expression level of another Wnt target gene, c-Ret.In the ICAT-/- kidneys which developed to E18.5 without any apparent defect, renal glomeruli, convoluted tubules and collecting ducts were decreased in density and showed abnormal structure.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy I, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan.

ABSTRACT
ICAT (Inhibitor of β-catenin and T cell factor) inhibits the interaction between β-catenin and TCF/LEF transcription factor and serves as a negative regulator of Wnt signaling. In a subset of ICAT knockout mice, significant delay in the ureteric bud branching and renal agenesis are observed. In order to examine the process of this developmental defect, molecular changes were analyzed in fetal ICAT-/- kidneys with a focus on Wnt-signaling associated factors. The protein level of active β-catenin was elevated in ICAT-/- kidneys. DNA microarray and immunohistochemical analyses revealed that the expression of a Wnt target gene Pitx-2 was enhanced in ICAT-/- kidneys. There was no genotypic difference in the expression level of another Wnt target gene, c-Ret. These results suggest that the enhancement of Pitx-2 expression induced by activated Wnt signaling leads to delays in ureteric bud branching and subsequent renal agenesis. In the ICAT-/- kidneys which developed to E18.5 without any apparent defect, renal glomeruli, convoluted tubules and collecting ducts were decreased in density and showed abnormal structure. ICAT may be required for various developmental stages during renal development.

No MeSH data available.


Related in: MedlinePlus