ABSTRACT
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.
Subject(s)
Chromosome Segregation/physiology , Microtubules/metabolism , Spindle Apparatus/metabolism , Animals , Brain/metabolism , Cell Cycle Proteins/metabolism , Chromosome Segregation/genetics , Female , Kinetochores/metabolism , Male , Mammals/genetics , Mice , Mice, Inbred C57BL , Microtubule-Associated Proteins/metabolism , Microtubules/physiology , Mitosis/physiology , Neural Stem Cells/metabolism , Neurogenesis/physiology , Pregnancy , Spindle Apparatus/physiologyABSTRACT
Centrosome clustering is a process frequently used by cancer cells with extra centrosomes to avoid multipolar divisions. How cell-intrinsic properties influence clustering is not entirely known. In this issue, Rhys et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201704102) report an unexpected link between clustering capacity and cortical contractility through E-cadherin and DDR1 proteins.
