Biology of Centrosomes and Genetic Instability Team, Curie Institute, PSL Research University, CNRS, UMR144, 12 rue Lhomond, Paris 75005, France.
Cell Biology of Mammalian Neurogenesis, Curie Institute, PSL Research University, CNRS, UMR144, 12 rue Lhomond, Paris 75005, France.
Curr Biol. 2019 Sep 23;29(18):2993-3005.e9. doi: 10.1016/j.cub.2019.07.061. Epub 2019 Sep 5.
A functional bipolar spindle is essential to segregate chromosomes correctly during mitosis. Across organisms and cell types, spindle architecture should be optimized to promote error-free divisions. However, it remains to be investigated whether mitotic spindle morphology adapts to changes in tissue properties, typical of embryonic development, in order to ensure different tasks, such as spindle positioning and chromosome segregation. We have characterized mitotic spindles in neural stem cells (NSCs) of the embryonic developing mouse neocortex. Surprisingly, we found a switch in spindle morphology from early to late neurogenic stages, which relies on an increase in inner spindle microtubule density and stability. Mechanistically, we identified the microtubule-associated protein TPX2 as one determinant of spindle shape, contributing not only to its robustness but also to correct chromosome segregation upon mitotic challenge. Our findings highlight a possible causal relationship between spindle architecture and mitotic accuracy with likely implications in brain size regulation.
有功能的双极纺锤体对于在有丝分裂过程中正确分离染色体至关重要。在不同的生物体和细胞类型中，纺锤体的结构应该得到优化，以促进无差错的分裂。然而，目前仍有待研究有丝分裂纺锤体形态是否会适应组织特性的变化，这些变化是胚胎发育过程中的典型特征，以确保不同的任务，如纺锤体定位和染色体分离。我们已经对胚胎发育的小鼠新皮质中的神经干细胞（NSCs）中的有丝分裂纺锤体进行了特征描述。令人惊讶的是，我们发现从早期到晚期神经发生阶段，纺锤体形态发生了转变，这依赖于内部纺锤体微管密度和稳定性的增加。从机制上讲，我们确定微管相关蛋白 TPX2 是纺锤体形状的一个决定因素，它不仅有助于纺锤体的稳定性，而且有助于在有丝分裂受到挑战时正确分离染色体。我们的发现强调了纺锤体结构与有丝分裂准确性之间可能存在因果关系，这可能对大脑大小的调节有重要意义。
