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Updated: May 12, 2026
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.
Abstract:
Yap is a transcriptional co-activator that regulates cell proliferation and apoptosis downstream of the Hippo kinase pathway. We investigated Yap function during mouse kidney development using a conditional knockout strategy that specifically inactivated Yap within the nephrogenic lineage. We found that Yap is essential for nephron induction and morphogenesis, surprisingly, in a manner independent of regulation of cell proliferation and apoptosis. We used microarray analysis to identify a suite of novel Yap-dependent genes that function during nephron formation and have been implicated in morphogenesis. Previous in vitro studies have indicated that Yap can respond to mechanical stresses in cultured cells downstream of the small GTPases RhoA. We find that tissue-specific inactivation of the Rho GTPase Cdc42 causes a severe defect in nephrogenesis that strikingly phenocopies loss of Yap. Ablation of Cdc42 decreases nuclear localization of Yap, leading to a reduction of Yap-dependent gene expression. We propose that Yap responds to Cdc42-dependent signals in nephron progenitor cells to activate a genetic program required to shape the functioning nephron.
Insights
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.
