Centrosome amplification causes microcephaly

Véronique Marthiens

doi:10.1038/ncb2746

2013-05-12

227

PRE

Paul-Gilloteaux, Perrine

Renata Basto *

DOI：10.1038/ncb2746

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摘要

En 中文

Centrosome amplification is a hallmark of human tumours. In flies, extra centrosomes cause spindle position defects that result in the expansion of the neural stem cell (NSC) pool and consequently in tumour formation. Here we investigated the consequences of centrosome amplification during mouse brain development and homeostasis. We show that centrosome amplification causes microcephaly due to inefficient clustering mechanisms, where NSCs divide in a multipolar fashion producing aneuploid cells that enter apoptosis. Importantly, we show that apoptosis inhibition causes the accumulation of highly aneuploid cells that lose their proliferative capacity and differentiate, thus depleting the pool of progenitors. Even if these conditions are not sufficient to halt brain development, they cause premature death due to tissue degeneration. Our results support an alternative concept to explain the etiology of microcephaly and show that centrosome amplification and aneuploidy can result in tissue degeneration rather than overproliferation and cancer.

Keyword:

CENTRIOLE DUPLICATION

SPINDLE ORIENTATION

EXTRA CENTROSOMES

NERVOUS-SYSTEM

MITOTIC ENTRY

PRIMARY CILIA

CELL

ANEUPLOIDY

CDK5RAP2

MUTATIONS

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期刊

Nature Cell Biology

IF:

19.1

论文数:

6.2K

被引数:

4.8W

机构

Universite PSL

学者数:

3.3W

论文数: 2.5W

被引数: 91

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