Augmin deficiency in neural stem cells causes p53-dependent apoptosis and aborts brain development

eLife

Sadanori Watanabe¹  Marcos Fariña-Mosquera²  Ricardo Viais²  Lluís Palenzuela²  Cristina Lacasa²  Marina Villamor-Payಠ Jens Lüders² 

[1] Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, Japan;Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain;

关键词: augmin;    spindle;    mitosis;    neural progenitor;    brain development;    microtubules;    Mouse;   

DOI  :  10.7554/eLife.67989

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Microtubules that assemble the mitotic spindle are generated by centrosomal nucleation, chromatin-mediated nucleation, and nucleation from the surface of other microtubules mediated by the augmin complex. Impairment of centrosomal nucleation in apical progenitors of the developing mouse brain induces p53-dependent apoptosis and causes non-lethal microcephaly. Whether disruption of non-centrosomal nucleation has similar effects is unclear. Here, we show, using mouse embryos, that conditional knockout of the augmin subunit Haus6 in apical progenitors led to spindle defects and mitotic delay. This triggered massive apoptosis and abortion of brain development. Co-deletion of Trp53 rescued cell death, but surviving progenitors failed to organize a pseudostratified epithelium, and brain development still failed. This could be explained by exacerbated mitotic errors and resulting chromosomal defects including increased DNA damage. Thus, in contrast to centrosomes, augmin is crucial for apical progenitor mitosis, and, even in the absence of p53, for progression of brain development.

【 授权许可】

CC BY