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Updated: Aug 19, 2026
Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction
M Albert Basson1, Simge Akbulut, Judy Watson-Johnson
1Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York, USA. albert.basson@kcl.ac.uk
Abstract:
Intercellular signaling molecules and their receptors, whose expression must be tightly regulated in time and space, coordinate organogenesis. Regulators of intracellular signaling pathways provide an additional level of control. Here we report that loss of the receptor tyrosine kinase (RTK) antagonist, Sprouty1 (Spry1), causes defects in kidney development in mice. Spry1(-/-) embryos have supernumerary ureteric buds, resulting in the development of multiple ureters and multiplex kidneys. These defects are due to increased sensitivity of the Wolffian duct to GDNF/RET signaling, and reducing Gdnf gene dosage correspondingly rescues the Spry1 null phenotype. We conclude that the function of Spry1 is to modulate GDNF/RET signaling in the Wolffian duct, ensuring that kidney induction is restricted to a single site. These results demonstrate the importance of negative feedback regulation of RTK signaling during kidney induction and suggest that failures in feedback control may underlie some human congenital kidney malformations.
Insights
Loss of Sprouty1 (Spry1) causes kidney development defects in mice by disrupting GDNF/RET signaling. This highlights the critical role of negative feedback in preventing congenital kidney malformations.
Area of Science:
- Developmental biology
- Molecular genetics
- Organogenesis
Background:
- Organogenesis relies on tightly regulated intercellular signaling.
- Intracellular signaling pathway regulators add another layer of control.
- Receptor tyrosine kinase (RTK) signaling is crucial for development.
Purpose of the Study:
- To investigate the role of Sprouty1 (Spry1), an RTK antagonist, in kidney development.
- To understand how Spry1 regulates signaling pathways involved in organogenesis.
- To explore the link between Spry1 function and congenital kidney malformations.
Main Methods:
- Utilized Spry1 knockout (Spry1-/-) mouse models.
- Analyzed kidney development and ureteric bud formation.
- Investigated the impact of GDNF/RET signaling pathway modulation.
- Assessed rescue effects by altering Gdnf gene dosage.
Main Results:
- Spry1 deficiency leads to supernumerary ureteric buds and multiplex kidneys.
- These defects stem from heightened Wolffian duct sensitivity to GDNF/RET signaling.
- Reducing Gdnf gene dosage rescues the Spry1 null phenotype.
Conclusions:
- Spry1 functions to modulate GDNF/RET signaling in the Wolffian duct during kidney induction.
- Spry1 ensures kidney induction is restricted to a single site.
- Failures in negative feedback regulation of RTK signaling may contribute to human congenital kidney malformations.
