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Dissection and Culture of Mouse Embryonic Kidney
Published on: May 17, 2017
Midline signaling regulates kidney positioning but not nephrogenesis through Shh
Piyush Tripathi1, Qiusha Guo, Yinqiu Wang
1Internal Medicine, Renal Division, Washington University School of Medicine, St Louis, MO 63110, USA.
Developmental Biology
|February 16, 2010
Summary
The notochord is not essential for kidney formation but is crucial for correct kidney positioning. Disrupting axial structures and Shh signaling leads to kidney fusion, offering insights into horseshoe kidney development.
Area of Science:
- Developmental Biology
- Renal Physiology
- Embryology
Background:
- The role of axial structures, particularly the notochord, in kidney development remains largely unexamined.
- Understanding the signaling pathways that guide kidney formation and positioning is critical for addressing congenital kidney defects.
Purpose of the Study:
- To investigate the direct role of the notochord and floor plate in metanephric kidney development.
- To elucidate the molecular mechanisms, specifically involving Sonic Hedgehog (Shh) signaling, underlying kidney positioning and fusion.
Main Methods:
- Utilized diphtheria toxin (DTA)-mediated cell ablation to disrupt notochord and floor plate function.
- Genetically inactivated Shh specifically in the notochord and floor plate.
- Analyzed kidney morphology and nephrogenesis in mutant embryos.
Main Results:
- Disruption of axial structures did not impede nephrogenesis but caused kidney fusion, mimicking horseshoe kidneys.
- Axial disruptions led to medial displacement of metanephric mesenchyme without affecting nephron formation.
- Depletion of axial Shh signaling was sufficient to induce kidney fusion, highlighting its critical role in kidney positioning.
Conclusions:
- The notochord is dispensable for nephrogenesis but essential for proper metanephric kidney positioning.
- Axial Shh signaling mediates the influence of axial structures on the mediolateral positioning of kidneys.
- These findings provide insights into the pathogenesis of horseshoe kidneys and congenital kidney defects originating from extra-renal signaling.
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