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Updated: Mar 22, 2026
Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
Prokineticin receptor 1 is required for mesenchymal-epithelial transition in kidney development
Himanshu Arora1, Mounia Boulberdaa1, Rehana Qureshi1
1Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg, Unité Mixte de Recherche (UMR) 7242, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France; and.
Abstract:
Identification of factors regulating renal development is important to understand the pathogenesis of congenital kidney diseases. Little is known about the molecular mechanism of renal development and functions triggered by the angiogenic hormone prokineticin-2 and its receptor, PKR1. Utilizing the Gata5 (G5)-Cre and Wilms tumor 1 (Wt1)(GFP)cre transgenic lines, we generated mutant mice with targeted PKR1 gene disruptions in nephron progenitors. These mutant mice exhibited partial embryonic and postnatal lethality. Kidney developmental defects in PKR(G5-/-) mice are manifested in the adult stage as renal atrophy with glomerular defects, nephropathy, and uremia. PKR1(Wt1-/-) embryos exhibit hypoplastic kidneys with premature glomeruli and necrotic nephrons as a result of impaired proliferation and increased apoptosis in Wt1(+) renal mesenchymal cells. PKR1 regulates renal mesenchymal-epithelial transition (MET) that is involved in formation of renal progenitors, regulating glomerulogenesis toward forming nephrons during kidney development. In the isolated embryonic Wt1(+) renal cells, overexpression or activation of PKR1 promotes MET defined by the transition from elongated cell to octagonal cell morphology, and alteration of the expression of MET markers via activating NFATc3 signaling. Together, these results establish PKR1 via NFATc3 as a crucial modifier of MET processing to the development of nephron. Our study should facilitate new therapeutic opportunities in human renal disorders.-Arora, H., Boulberdaa, M., Qureshi, R., Bitirim, V., Messadeq, N., Dolle, P., Nebigil, C. G. Prokineticin receptor 1 is required for mesenchymal-epithelial transition in kidney development.
Insights
Prokineticin receptor 1 (PKR1) is crucial for kidney development, regulating mesenchymal-epithelial transition (MET) in nephron formation. Its disruption leads to congenital kidney diseases, offering potential therapeutic targets.
Area of Science:
- Developmental Biology
- Nephrology
- Molecular Biology
Background:
- Congenital kidney diseases stem from impaired renal development, yet molecular mechanisms remain unclear.
- The role of prokineticin-2 and its receptor, PKR1, in kidney development is largely unknown.
Purpose of the Study:
- To investigate the function of Prokineticin receptor 1 (PKR1) in kidney development and its role in congenital kidney diseases.
- To elucidate the molecular mechanisms by which PKR1 regulates renal development, specifically mesenchymal-epithelial transition (MET).
Main Methods:
- Generated and analyzed mutant mice with targeted PKR1 gene disruptions in nephron progenitors using Gata5-Cre and Wt1(GFP)cre transgenic lines.
- Examined kidney morphology, cell proliferation, apoptosis, and cell morphology changes in isolated embryonic renal cells.
- Investigated the role of NFATc3 signaling in PKR1-mediated MET.
Main Results:
- PKR1 disruption in mice caused partial lethality and severe kidney defects, including renal atrophy, glomerular defects, nephropathy, and uremia.
- PKR1 deficiency in Wt1(+) renal mesenchymal cells led to hypoplastic kidneys, premature glomeruli, and necrotic nephrons due to impaired proliferation and increased apoptosis.
- PKR1 activation promotes MET in renal cells by altering cell morphology and regulating MET markers via NFATc3 signaling.
Conclusions:
- PKR1 is essential for regulating mesenchymal-epithelial transition (MET) during kidney development, crucial for nephron formation.
- PKR1 acts through NFATc3 signaling to control MET, highlighting a key pathway in kidney development.
- These findings provide insights into congenital kidney diseases and suggest potential therapeutic strategies targeting the PKR1 pathway.
