Amanda Knoten

Arquint

Astrinidis

Battini

Bettencourt-Dias

Bhaskar

Boehlke

Boletta

Brito

Brown

Burtey

Chang-Panesso

Chen

Coelho

Cosenza

Davenport

Dere

Distefano

Fisher

Ganem

Godinho

Goto

Habedanck

Hartman

Hendry

Hoshi

Jain

Janssen

Jinzhi Wang

Jonassen

Keefe Davis

Kobayashi

Krämer

Kulukian

Kyuhwan Shim

Lai Kuan Dionne

Levine

Mahjoub

Majumdar

Marthiens

Masato Hoshi

Masyuk

Moe R. Mahjoub

Mugford

Mundlos

Nano

Nigg

Ogden

Patel

Quintyne

Renata Basto

Roselli

Saifudeen

Sanjay Jain

Schmidt-Ott

Serçin

Shao

Sharma

Shillingford

Silkworth

Sillibourne

Simons

Srivastava

Takakura

Tammachote

Tao Cheng

Veronique Marthiens

Vitre

Werner

Yoder

Zhao

English

Dionne, Lai Kuan

Shim, Kyuhwan

Hoshi, Masato

Cheng, Tao

Wang, Jinzhi

Marthiens, Veronique

Knoten, Amanda

Basto, Renata

Jain, Sanjay

Mahjoub, Moe

HAL: Hyper Article en Ligne

Centrosome amplification disrupts renal development and causes cystogenesis

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.</jats:p

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The Journal of Cell Biology

International audienceCentrosome 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

International audienceRockefeller University Press 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

Centrosome amplification disrupts renal development and causes cystogenesis

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