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Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
Yap- and Cdc42-dependent nephrogenesis and morphogenesis during mouse kidney development
Antoine Reginensi1, Rizaldy P Scott, Alex Gregorieff
1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Plos Genetics
|April 5, 2013
Summary
YAP (Yes-associated protein) is crucial for kidney development, independent of cell division or death. It works with Cdc42 to regulate gene expression for forming functioning nephrons.
Area of Science:
- Developmental biology
- Molecular biology
- Genetics
Background:
- The Hippo pathway kinase regulates cell proliferation and apoptosis via the transcriptional co-activator YAP.
- YAP's role in kidney development and its upstream regulators are not fully understood.
Purpose of the Study:
- To investigate the function of YAP in mouse kidney development.
- To identify YAP-dependent genes involved in nephrogenesis.
- To explore the relationship between YAP and Rho GTPases in kidney development.
Main Methods:
- Conditional knockout strategy to inactivate YAP in the nephrogenic lineage.
- Microarray analysis to identify YAP-dependent genes.
- Tissue-specific inactivation of the Rho GTPase Cdc42.
Main Results:
- YAP is essential for nephron induction and morphogenesis, independent of cell proliferation and apoptosis.
- Microarray analysis identified novel YAP-dependent genes involved in morphogenesis.
- Inactivation of Cdc42 phenocopies YAP loss, reduces nuclear YAP localization, and decreases YAP-dependent gene expression.
Conclusions:
- YAP plays a critical role in kidney development by regulating morphogenesis through a pathway involving Cdc42.
- Cdc42 signaling influences YAP activity and downstream gene expression in nephron progenitor cells.
- This study reveals a novel mechanism for YAP in coordinating kidney development.
