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Kidney Week

Abstract: FR-PO965

Consequences of Centrosome Numerical Aberrations in Cystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic


  • Mahjoub, Moe, Washington University School of Medicine/Nephrology, ST LOUIS, Missouri, United States
  • Cheng, Tao, Washington University School of Medicine/Nephrology, ST LOUIS, Missouri, United States
  • Dionne, Lai Kuan, Washington University St. Louis, St. Louis, Missouri, United States
  • Shim, Kyuhwan, Washington University School of Medicine/Nephrology, ST LOUIS, Missouri, United States

The centrosome and primary cilium act together as a cellular “hub” to regulate several important developmental signaling pathways. Defects in centrosome biogenesis can result in numerical aberrations in centrosome-cilium number, resulting in cells that either lose these structures or assemble too many. Importantly, numerical aberrations in centrosomes have been reported in various types of cystic kidney disease including ADPKD, nephronophthisis, and cystic kidneys of ciliopathy patients. What remains unknown are the consequences of centrosome numerical aberrations during embryonic kidney development, adult kidney homeostasis, and after renal injury.


To ablate centrosomes we utilized mice harboring a conditional allele of Cep120 (Cep120f/f), which we previously showed is essential for centrosome formation. To increase centrosome number, we used a transgenic mouse with a conditional overexpression allele of the kinase Plk4 (Tg::mChPlk4), known as the master regulator of centrosome duplication. Cep120f/for Tg::mChPlk4 mice were crossed with Six2-Cre or Hoxb7-Cre animals to cause ablation/amplification of centrosomes in the metanephric mesenchyme or ureteric bud epithelium, respectively. Finally, these mice were mated with Slc34a1-CreERTor Ksp-CreERTto induce overexpression/loss of centrosomes in fully developed kidneys.


Increasing centrosome number perturbed mitotic spindle morphology, ciliary assembly, and signaling pathways essential for growth of renal progenitors. This resulted in defective branching morphogenesis, renal hypoplasia, and rapid cystogenesis after birth. Moreover, centrosome amplification sensitized kidneys in adult mice, causing cystogenesis following ischemic renal injury. In contrast, loss of centrosomes did not have an adverse effect on progenitor cell proliferation, nor caused renal hypoplasia. In fact, loss of centrosomes resulted in enlarged kidneys that became rapidly cystic. Remarkably, loss of centrosomes during kidney homeostasis did not affect overall kidney function, nor cause cyst formation.


Our results highlight the heterogeneity of response to centrosomal numerical aberrations in different renal cells types and developmental stages. These results indicate that the underlying signaling changes are likely to be different, and suggest that therapeutic strategies will have to be developed separately for each case.


  • NIDDK Support