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Updated: Aug 14, 2026
Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
Perturbation of RET signaling in the embryonic kidney
C W Ehrenfels1, P J Carmillo, O Orozco
1Department of Molecular Genetics, Biogen, Inc., Cambridge, Massachusetts 02142, USA.
Abstract:
We have used a RET-Ig fusion protein to disrupt signaling in the rat embryonic kidney development pathway. Treatment of embryonic kidney organ cultures with RET-Ig results in a decrease in branching of the ureteric bud and a down regulation in expression of the Wnt-11, Wnt-4, and ld genes. These data suggest that Wnt-11, Wnt-4, and ld function downstream of RET signaling in normal development. Expression of BMP-7, shh, and ptc were uneffected by RET-Ig treatment, implying that these genes are regulated independently of ret. We have also performed immunohistochemistry with a GFR alpha-1 specific polyclonal antisera to localize GFR alpha-1 protein expression in the developing kidney.
Insights
RET signaling disruption in rat embryonic kidneys reduced ureteric bud branching and Wnt gene expression. This indicates Wnt-11, Wnt-4, and ld function downstream of RET in kidney development.
Area of Science:
- Developmental biology
- Molecular biology
- Genetics
Background:
- Ret signaling pathway is crucial for embryonic kidney development.
- Understanding the molecular mechanisms downstream of Ret is essential for comprehending kidney organogenesis.
Purpose of the Study:
- To investigate the role of RET signaling in rat embryonic kidney development.
- To identify downstream targets of RET signaling in the developing kidney.
Main Methods:
- Utilized a RET-Ig fusion protein to inhibit RET signaling in embryonic kidney organ cultures.
- Analyzed ureteric bud branching and gene expression patterns (Wnt-11, Wnt-4, ld, BMP-7, shh, ptc).
- Performed immunohistochemistry to localize GFR alpha-1 protein expression.
Main Results:
- RET-Ig treatment decreased ureteric bud branching.
- Downregulation of Wnt-11, Wnt-4, and ld gene expression observed.
- Expression of BMP-7, shh, and ptc remained unaffected by RET-Ig treatment.
- Localized GFR alpha-1 protein expression in the developing kidney.
Conclusions:
- Wnt-11, Wnt-4, and ld function downstream of RET signaling in embryonic kidney development.
- BMP-7, shh, and ptc are regulated independently of RET signaling.
- RET signaling plays a key role in regulating ureteric bud branching and specific gene expression during kidney organogenesis.
