Abstract: PO0608
Expression Pattern of the Runt-Related Transcription Factor (RUNX) Family and the Role of RUNX1 During Kidney Development
Session Information
- Development, Stem Cells, and Regenerative Medicine
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 500 Development, Stem Cells, and Regenerative Medicine
Authors
- Sakamoto, Keiko, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Kitai, Yuichiro, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Yanagita, Motoko, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Background
RUNX family plays critical roles during the developmental process in multiple organs. The mammalian RUNX family consist of RUNX1, RUNX2 and RUNX3, each of them has distinct tissue-specific expression and function but also has a redundancy. Here, we examined the distribution of RUNX family in the kidney. We also assessed the involvement of RUNX1 during renal development in the conditional knockout mice using Cre-LoxP strategy.
Methods
We examined the temporal and spatial expression pattern of RUNX family in the kidney by immunostaining and qPCR analysis. In order to analyze the role of RUNX1 in kidney development, we utilized HoxB7-Cre mice and R26CreERT2 mice. To induce activation of CreERT2, we administered tamoxifen to pregnant mothers at E12.5 and analyzed the embryos at E16.5. Long-term observation was impossible due to the severe anemia caused by hematological toxicity of the systemic activation of CreERT2.
Results
In the neonatal kidney, RUNX1 was strongly expressed in the uretic bud (UB) tip and also weakly expressed in the distal portion of renal vesicle, comma body, and S shaped body. RUNX1 was also expressed in the pelvic urothelium and immune cells. RUNX1 expression in the UB tips was detectable from E13.5 and disappeared by P7. In contrast, RUNX2 was restricted in the stroma firstly detected from E15.5 and was strongly expressed in both cortical and medullary fibroblasts at P2. RUNX3 was only expressed in the immune cells. There was no difference in the number of UB branching or Six2+ nephron progenitor cells per UB tip in Runx1fl/fl: HoxB7-Cre mice, which lack Runx1 expression in UB. Further analysis utilizing Runx1fl/fl: R26CreERT2 mice showed no obvious abnormality. In addition, neither RUNX2 nor RUNX3 compensated the loss of RUNX1 in deficient embryos.
Conclusion
We precisely analyzed the unique expression pattern of RUNX family during kidney development and identified RUNX1 as the marker of UB tip and RUNX2 as the marker of fibroblasts in the embryonic kidneys, although RUNX1 was dispensable for nephrogenesis.
Expression of RUNX1 and RUNX2 in the developing kidney