Spindle Scaling Is Governed by Cell Boundary Regulation of Microtubule Nucleation.

Cellular organelles such as the mitotic spindle adjust their size to the dimensions of the cell. It is widely understood that spindle scaling is governed by regulation of microtubule polymerization. Here, we use quantitative microscopy in living zebrafish embryos and Xenopus egg extracts in combination with theory to show that microtubule polymerization dynamics are insufficient to scale spindles and only contribute below a critical cell size. In contrast, microtubule nucleation governs spindle scaling for all cell sizes. We show that this hierarchical regulation arises from the partitioning of a nucleation inhibitor to the cell membrane. Our results reveal that cells differentially regulate microtubule number and length using distinct geometric cues to maintain a functional spindle architecture over a large range of cell sizes.

How to tune spindle size relative to cell size?

Cells need to regulate the size and shape of their organelles for proper function. For example, the mitotic spindle adapts its size to changes in cell size over several orders of magnitude, but we lack a mechanistic understanding of how this is achieved. Here, we review our current knowledge of how small and large spindles assemble and ask which microtubule-based biophysical processes (nucleation, polymerization dynamics, transport) may be responsible for spindle size regulation. Finally, we review possible cell-scale mechanisms that put spindle size under the regulation of cell size.