Centrosome amplification disrupts renal development and causes cystogenesis'

Lai Kuan Dionne, Kyuhwan Shim, Masato Hoshi, Tao Cheng, Jinzhi Wang, Veronique Marthiens, Amanda Knoten, Renata Basto, Sanjay Jain, Moe R. Mahjoub

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Centrosome number is tightly controlled to ensure proper ciliogenesis, mitotic spindle assembly, and cellular homeostasis. Centrosome amplification (the formation of excess centrosomes) has been noted in renal cells of patients and animal models of various types of cystic kidney disease. Whether this defect plays a causal role in cystogenesis remains unknown. Here, we investigate the consequences of centrosome amplification during kidney development, homeostasis, and after injury. Increasing centrosome number in vivo perturbed proliferation and differentiation of renal progenitors, resulting in defective branching morphogenesis and renal hypoplasia. Centrosome amplification disrupted mitotic spindle morphology, ciliary assembly, and signaling pathways essential for the function of renal progenitors, highlighting the mechanisms underlying the developmental defects. Importantly, centrosome amplification was sufficient to induce rapid cystogenesis shortly after birth. Finally, we discovered that centrosome amplification sensitized kidneys in adult mice, causing cystogenesis after ischemic renal injury. Our study defines a new mechanism underlying the pathogenesis of renal cystogenesis, and identifies a potentially new cellular target for therapy.

Original languageEnglish
Pages (from-to)2485-2501
Number of pages17
JournalJournal of Cell Biology
Volume217
Issue number7
DOIs
StatePublished - Jul 2018

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