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Centrosome amplification disrupts renal development and causes cystogenesis.


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.

SUBMITTER: Dionne LK 

PROVIDER: S-EPMC6028550 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Centrosome amplification disrupts renal development and causes cystogenesis.

Dionne Lai Kuan LK   Shim Kyuhwan K   Hoshi Masato M   Cheng Tao T   Wang Jinzhi J   Marthiens Veronique V   Knoten Amanda A   Basto Renata R   Jain Sanjay S   Mahjoub Moe R MR  

The Journal of cell biology 20180612 7


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 cen  ...[more]

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