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Centrosome amplification disrupts renal development and causes cystogenesis.
Lai Kuan Dionne1, Kyuhwan Shim1, Masato Hoshi1
1Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
The Journal of Cell Biology
|June 14, 2018
Summary
Centrosome amplification, an excess of centrosomes, causes kidney developmental defects and cyst formation. This finding reveals a new mechanism for kidney cyst disease and a potential therapeutic target.
Area of Science:
- Cell Biology
- Developmental Biology
- Nephrology
Background:
- Centrosome number is critical for cell function, including ciliogenesis and mitosis.
- Centrosome amplification is observed in cystic kidney diseases, but its causal role is unclear.
Purpose of the Study:
- To investigate the role of centrosome amplification in kidney development, homeostasis, and disease.
- To elucidate the mechanisms by which centrosome amplification impacts renal cells.
Main Methods:
- In vivo studies of centrosome amplification in mouse models.
- Analysis of renal progenitor proliferation, differentiation, and signaling pathways.
- Assessment of kidney development, cystogenesis, and response to injury.
Main Results:
- Centrosome amplification in vivo impaired renal progenitor development, causing hypoplasia.
- Excess centrosomes disrupted mitotic spindles, ciliary assembly, and essential signaling.
- Centrosome amplification induced rapid cystogenesis postnatally and sensitized adult kidneys to injury.
Conclusions:
- Centrosome amplification is a causal factor in renal cystogenesis.
- This defect disrupts kidney development and repair, offering a novel therapeutic target for cystic kidney diseases.
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