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Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
PTEN modulates GDNF/RET mediated chemotaxis and branching morphogenesis in the developing kidney
Doyeob Kim1, Gregory R Dressler
1Department of Pathology, University of Michigan, MSRB1, BSRB 2049, 109 Zina Pitcher Dr., Ann Arbor, MI 48109, USA.
Developmental Biology
|June 2, 2007
Summary
The RET receptor tyrosine kinase pathway is crucial for kidney development. PTEN loss disrupts this pathway, affecting kidney branching morphogenesis and cell migration during development.
Area of Science:
- Developmental Biology
- Molecular Biology
- Cell Signaling
Background:
- The RET receptor tyrosine kinase, activated by GDNF, regulates ureteric bud epithelial outgrowth and invasion in kidney development.
- RET activation drives chemotaxis in renal and enteric precursor cells, mediating invasion into GDNF-rich tissues.
- Phosphatidylinositol 3-kinase (PI3K) signaling, generating PI(3,4,5) triphosphate, is a potential downstream pathway for RET-mediated chemotaxis.
Purpose of the Study:
- To investigate the role of PTEN in regulating RET-mediated cell migration and chemotaxis.
- To explore the impact of PTEN on RET signaling pathways.
- To determine the effect of PTEN loss on kidney branching morphogenesis.
Main Methods:
- Cell culture assays to assess RET-mediated cell migration and chemotaxis.
- Analysis of inositol triphosphate localization upon RET activation.
- Examination of kidney branching morphogenesis in developing mouse models with altered PTEN function.
Main Results:
- PTEN was found to suppress RET-mediated cell migration and chemotaxis in vitro.
- RET activation led to asymmetric localization of inositol triphosphates.
- Loss of PTEN function resulted in altered patterns of branching morphogenesis in developing mouse kidneys.
Conclusions:
- The PI3K/PTEN signaling axis plays a critical role in modulating RET-driven epithelial branching patterns.
- PTEN acts as a suppressor of RET-mediated chemotaxis, influencing cell migration.
- These findings highlight the importance of the PI3K/PTEN pathway in guiding developmental processes regulated by RET signaling.
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